Surgery for gastroesophageal reflux disease with Gaucher disease type 2.

Gaucher disease, the most common lysosomal storage disease, is sometimes complicated with gastroesophageal reflux disease (GERD). The present patient was a 136-day-old Japanese boy with Gaucher disease type 2. Enzyme replacement therapy and chemical chaperone therapy were successful for the skin disorders, joint contractures, hepatosplenomegaly and thrombocytopenia, but he also had GERD. Accordingly, a Nissen fundoplication with gastrostomy was performed. There was no vulnerability of organs, easy bleeding or difficulty of maintaining the visual field because of hepatosplenomegaly during operation. In the perioperative period, there was no prolonged wound healing or infection. GERD was improved. In the near future, the number of long-term survivors of Gaucher disease will increase due to improvements in medical therapy. Therefore, it is expected that the number of patients requiring fundoplication will also increase. In patients with successful medical therapy, surgical fundoplication can be safely and effectively performed.

    Gaucher disease
    DIAGNOSIS

, the most common

    lysosomal storage disease
    DIAGNOSIS

, is sometimes complicated with

    gastroesophageal reflux disease (GERD)
    DIAGNOSIS

. The present patient was a

    136-day-old
    AGE

    Japanese
    ETHNICITY

    boy
    GENDER

 with

    Gaucher disease type 2
    DIAGNOSIS

.

    Enzyme replacement therapy
    MEDICATION

 and

    chemical chaperone therapy
    MEDICATION

 were successful for the

    skin disorders
    SYMPTOMS

,

    joint contractures
    SYMPTOMS

,

    hepatosplenomegaly
    SYMPTOMS

 and

    thrombocytopenia
    BIOCHEMICAL

, but

    he
    GENDER

 also had

    GERD
    DIAGNOSIS

. Accordingly, a

    Nissen fundoplication with gastrostomy
    MEDICATION

 was performed. There was

    no vulnerability of organs, easy bleeding or difficulty of maintaining the visual field because of hepatosplenomegaly during operation
    NEG_FINDINGS

. In the perioperative period, there was

    no prolonged wound healing or infection
    NEG_FINDINGS

.

    GERD was improved
    SYMPTOMS

. In the near future, the number of long-term survivors of

    Gaucher disease
    DIAGNOSIS

 will increase due to improvements in medical therapy. Therefore, it is expected that the number of patients requiring

    fundoplication
    MEDICATION

 will also increase. In patients with successful medical therapy,

    surgical fundoplication
    MEDICATION

 can be safely and effectively performed.

Gaucher disease
lysosomal storage disease
gastroesophageal reflux disease (GERD)
Gaucher disease type 2
GERD
Gaucher disease

Enzyme replacement therapy
chemical chaperone therapy
Nissen fundoplication with gastrostomy
fundoplication
surgical fundoplication

skin disorders
joint contractures
hepatosplenomegaly
GERD was improved


[Treatment of Gaucher disease with allogeneic hematopoietic stem cell transplantation: report of three cases and review of literatures].

To explore the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Gaucher disease.

The clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried.

Three children with Gaucher disease, all were female, received UCBT. These patients' age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received splenectomy before UCBT. The pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG), and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil (MMF) wee used for prophylaxis of acute graft versus host disease (aGVHD). The dose of cord blood stem cell nucleated cell counts was 9.7 × 10⁷ /kg,11.9 × 10⁷ /kg and 7.6 × 10⁷/kg respectively. The dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 10⁵/kg , 3.5 × 10⁵/kg and 3.2 × 10⁵/kg respectively. The day of granulocytes exceeding 0.5 × 10⁹/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 10⁹/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of β-glucocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In case 1 immune thrombocytopenia occurred at five month after transplantation unresponding to steroids and mesenchymal stem cells infusion was administered and his platelet in routine blood test recovered to normal. But the patient died because she was infected with varicella-zoster virus out of hospital at nine month after transplantation and the level of β-glucocerebrosidase was normal before death and chronic GVHD (cGVHD) was not found. The case 2 is now in 19th month after transplantation and his level of β-glucocerebrosidase was normal. cGVHD was not found. The patient is currently free of disease. The case 3 was in 9th month after transplantation and his level of β-glucocerebrosidase was normal. cGVHD was found at 112 day after transplantation and was localized and could be controlled by hormonal therapy. The patient is currently free of disease. Three patients' size of liver was significantly reduced after their level of β-glucocerebrosidase ecovered. There were 50 cases with Gaucher disease who were treated with allo-HSCT in the literature and none of them were reported from China. Disease-free survival rate of patients treated with allo-HSCT for Gaucher disease was 85%. In all reports, there were 31 cases who had information of typing of Gaucher disease, of whom 22 cases had type 1 and 9 cases had type 3. Twenty-nine cases had information of survival, of whom 24 cases survived and 5 cases died of infection. Fifteen cases had data of engraftment, 2 of whom had graft failure and one had late graft failure.Glucocerebrosidase recovered to normal in 25 of 31 cases who had relevant data, in one of whom with late graft failure the enzyme recovered to normal 3 month after transplantation, but his enzyme decreased to the initial level 9 month after transplantation. Along with enzyme level's recovery to normal, in a part of cases bone pain and hepatomegaly were relieved and growth delay was improved.

The unrelated UCBT may be a form of treatment that offers the potential of permanent cure and a procedure with possible long-term benefits in patients with Gaucher disease.

To explore the efficacy of

    unrelated umbilical cord blood transplantation (UCBT)
    MEDICATION

 in the treatment of

    Gaucher disease
    DIAGNOSIS

.

The clinical characteristics of three

    children
    AGE

 with

    Gaucher disease
    DIAGNOSIS

 underwent

    UCBT
    MEDICATION

 in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on

    allogeneic hematopoietic stem cell transplantation (allo-HSCT)
    MEDICATION

 in the treatment of

    Gaucher disease
    DIAGNOSIS

 was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried.

Three

    children
    AGE

 with

    Gaucher disease
    DIAGNOSIS

, all were

    female
    GENDER

,

    received UCBT
    MEDICATION

. These patients'

    age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years
    AGE

, respectively. The second case received the

    second transplantation
    MEDICATION

. The first and third case

    received splenectomy before UCBT
    MEDICATION

. The

    pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG)
    MEDICATION

, and for the patient

    received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG
    MEDICATION

.

    Cyclosporine and mycophenolate mofetil (MMF)
    MEDICATION

 wee used for

    prophylaxis of acute graft versus host disease (aGVHD)
    DIAGNOSIS

. The

    dose of cord blood stem cell nucleated cell counts was 9.7 × 10⁷ /kg,11.9 × 10⁷ /kg and 7.6 × 10⁷/kg respectively
    MEDICATION

. The

    dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 10⁵/kg , 3.5 × 10⁵/kg and 3.2 × 10⁵/kg respectively
    MEDICATION

. The day of

    granulocytes exceeding 0.5 × 10⁹/L
    BIOCHEMICAL

 was day 11, 12 and 19 after

    transplantation
    MEDICATION

, respectively. The day of

    platelets exceeding 20 × 10⁹/L
    BIOCHEMICAL

 was day 14, 33 and 74 after

    transplantation
    MEDICATION

, respectively. At one month after

    transplantation
    MEDICATION

 the

    rate of chimerism was over 95%
    SYMPTOMS

 and all patients got

    donor complete chimerism
    SYMPTOMS

. The

    level of β-glucocerebrosidase recovered to normal
    BIOCHEMICAL

 at one month after

    transplantation
    MEDICATION

. During

    transplantation
    MEDICATION

, all patients developed

    cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia
    DIAGNOSIS

. In case 1

    immune thrombocytopenia occurred
    BIOCHEMICAL

 at five month after

    transplantation
    MEDICATION

    unresponding to steroids
    NEG_FINDINGS

 and

    mesenchymal stem cells infusion
    MEDICATION

 was administered and

    his
    GENDER

    platelet in routine blood test recovered to normal
    BIOCHEMICAL

. But the patient

    died
    SYMPTOMS

 because

    she
    GENDER

 was

    infected with varicella-zoster virus
    DIAGNOSIS

 out of hospital at nine month after

    transplantation
    MEDICATION

 and the

    level of β-glucocerebrosidase was normal
    NEG_FINDINGS

 before

    death
    SYMPTOMS

 and

    chronic GVHD (cGVHD) was not found
    NEG_FINDINGS

. The case 2 is now in 19th month after

    transplantation
    MEDICATION

 and

    his
    GENDER

    level of β-glucocerebrosidase was normal
    NEG_FINDINGS

.

    cGVHD was not found
    NEG_FINDINGS

. The patient is currently

    free of disease
    NEG_FINDINGS

. The case 3 was in 9th month after

    transplantation
    MEDICATION

 and

    his
    GENDER

    level of β-glucocerebrosidase was normal
    NEG_FINDINGS

.

    cGVHD
    DIAGNOSIS

 was found at 112 day after

    transplantation
    MEDICATION

 and was localized and could be controlled by

    hormonal therapy
    MEDICATION

. The patient is currently

    free of disease
    NEG_FINDINGS

. Three patients'

    size of liver was significantly reduced
    SYMPTOMS

 after their

    level of β-glucocerebrosidase ecovered
    BIOCHEMICAL

. There were 50 cases with

    Gaucher disease
    DIAGNOSIS

 who were treated with

    allo-HSCT
    MEDICATION

 in the literature and none of them were reported from

    China
    ETHNICITY

.

    Disease-free
    NEG_FINDINGS

 survival rate of patients treated with

    allo-HSCT
    MEDICATION

 for

    Gaucher disease
    DIAGNOSIS

 was 85%. In all reports, there were 31 cases who had information of typing of

    Gaucher disease
    DIAGNOSIS

, of whom 22 cases had

    type 1
    DIAGNOSIS

 and 9 cases had

    type 3
    DIAGNOSIS

. Twenty-nine cases had information of survival, of whom 24 cases survived and 5 cases

    died of infection
    SYMPTOMS

. Fifteen cases had data of

    engraftment
    MEDICATION

, 2 of whom had

    graft failure
    SYMPTOMS

 and one had

    late graft failure
    SYMPTOMS

.

    Glucocerebrosidase recovered to normal
    BIOCHEMICAL

 in 25 of 31 cases who had relevant data, in one of whom with

    late graft failure
    SYMPTOMS

 the

    enzyme recovered to normal 3 month after transplantation
    BIOCHEMICAL

, but

    his
    GENDER

    enzyme decreased to the initial level 9 month after transplantation
    BIOCHEMICAL

. Along with

    enzyme level's recovery to normal
    BIOCHEMICAL

, in a part of cases

    bone pain
    SYMPTOMS

 and

    hepatomegaly
    SYMPTOMS

 were relieved and

    growth delay was improved
    SYMPTOMS

.

The

    unrelated UCBT
    MEDICATION

 may be a form of treatment that offers the potential of

    permanent cure
    MEDICATION

 and a procedure with possible long-term benefits in patients with

    Gaucher disease
    DIAGNOSIS

.

rate of chimerism was over 95%
donor complete chimerism
died
death
size of liver was significantly reduced
died of infection
graft failure
late graft failure
late graft failure
bone pain
hepatomegaly
growth delay was improved


Lung Transplantation in Gaucher Disease: A Learning Lesson in Trying to Avoid Both Scylla and Charybdis.

Gaucher disease (GD), a lysosomal storage disorder, may result in end-stage lung disease. We report successful bilateral lung transplantation in a 49-year-old woman with GD complicated by severe pulmonary hypertension and fibrotic changes in the lungs. Before receiving the lung transplant, the patient was undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil). She had a history of splenectomy, severe bone disease, and renal involvement, all of which were related to GD and considered as relative contraindications for a lung transplantation. In the literature, lung transplantation has been suggested for severe pulmonary involvement in GD but has been reported only once in a child. To our knowledge, until now, no successful procedure has been reported in adults, and no reports deal with the severe potential posttransplantation complications specifically related to GD.

    Gaucher disease (GD)
    DIAGNOSIS

, a

    lysosomal storage disorder
    DIAGNOSIS

, may result in

    end-stage lung disease
    DIAGNOSIS

. We report

    successful bilateral lung transplantation
    MEDICATION

 in a

    49-year-old
    AGE

    woman
    GENDER

 with

    GD
    DIAGNOSIS

 complicated by

    severe pulmonary hypertension
    SYMPTOMS

 and

    fibrotic changes in the lungs
    SYMPTOMS

. Before

    receiving the lung transplant
    MEDICATION

, the patient was

    undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil)
    MEDICATION

.

    She
    GENDER

 had a

    history of splenectomy
    MEDICATION

,

    severe bone disease
    SYMPTOMS

, and

    renal involvement
    SYMPTOMS

, all of which were related to

    GD
    DIAGNOSIS

 and considered as

    relative contraindications for a lung transplantation
    NEG_FINDINGS

. In the literature,

    lung transplantation
    MEDICATION

 has been suggested for

    severe pulmonary involvement
    SYMPTOMS

 in

    GD
    DIAGNOSIS

 but has been reported only once in a

    child
    AGE

. To our knowledge, until now, no successful procedure has been reported in

    adults
    AGE

, and no reports deal with the

    severe potential posttransplantation complications
    SYMPTOMS

 specifically related to

    GD
    DIAGNOSIS

.

Gaucher disease (GD)
lysosomal storage disorder
end-stage lung disease
GD
GD
GD
GD


Bilateral Femoral Osteolytic Lesions in a Patient with Type 3 Gaucher Disease.

Type 3 Gaucher disease (GD) manifests with hematologic, neurological and skeletal involvement including Erlenmeyer flask bone deformities, osteopenia, painful bone crises and fractures. We describe bilateral symmetric osteolytic lesions in a 22 year old with type 3 GD, chronically treated with enzyme replacement therapy. These atypical bone findings, previously reported in two similar patients with type 3 GD, expand our understanding of the evolving natural history of GD in the post-treatment era.

    Type 3 Gaucher disease (GD)
    DIAGNOSIS

 manifests with

    hematologic, neurological and skeletal involvement
    SYMPTOMS

 including

    Erlenmeyer flask bone deformities
    SYMPTOMS

,

    osteopenia
    SYMPTOMS

,

    painful bone crises
    SYMPTOMS

 and

    fractures
    SYMPTOMS

. We describe

    bilateral symmetric osteolytic lesions
    SYMPTOMS

 in a

    22 year old
    AGE

 with

    type 3 GD
    DIAGNOSIS

,

    chronically treated with enzyme replacement therapy
    MEDICATION

. These

    atypical bone findings
    SYMPTOMS

, previously reported in two similar patients with

    type 3 GD
    DIAGNOSIS

, expand our understanding of the evolving natural history of

    GD
    DIAGNOSIS

 in the post-treatment era.

Type 3 Gaucher disease (GD)
type 3 GD
type 3 GD
GD


CD4+CD25 high Foxp3+ Treg deficiency in a Brazilian patient with Gaucher disease and lupus nephritis.

Gaucher Disease (GD) is a rare autosomal recessive disorder caused by the deficient activity of beta-glucocerebrosidase. GD is one of the lysosomal storage diseases with the most remarkable alterations in the immune system, and that may manifest clinically as autoimmune disorders and malignancy. We reported the immunological evaluation of a patient with GD and lupus nephritis. Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio, low levels of IgM and normal B cells were found when compared to reference values in a Brazilian population. Absence ofCD4(+)CD25(high)Foxp3(+) Treg and high levels of total NKT, iNKT cells and CD8(+) iNKT subsets were also observed when compared to the healthy control and GD patient without lupus nephritis. Treg subset and CD8(+) iNKT abnormalities might be involved in severe lupus nephritis in a GD patient. We conclude by emphasizing the importance of the immunological evaluation on early diagnosis of autoimmunity contributing to reduce mortality and morbidity of these patients.

    Gaucher Disease (GD)
    DIAGNOSIS

 is a

    rare autosomal recessive disorder
    GENETICS

 caused by the

    deficient activity of beta-glucocerebrosidase
    BIOCHEMICAL

.

    GD
    DIAGNOSIS

 is one of the

    lysosomal storage diseases
    DIAGNOSIS

 with the most remarkable

    alterations in the immune system
    SYMPTOMS

, and that may manifest clinically as

    autoimmune disorders
    DIAGNOSIS

 and

    malignancy
    DIAGNOSIS

. We reported the

    immunological evaluation
    PARACLINICAL

 of a patient with

    GD
    DIAGNOSIS

 and

    lupus nephritis
    DIAGNOSIS

.

    Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio
    BIOCHEMICAL

,

    low levels of IgM
    BIOCHEMICAL

 and

    normal B cells
    BIOCHEMICAL

 were found when compared to reference values in a Brazilian population.

    Absence ofCD4(+)CD25(high)Foxp3(+) Treg
    GENETICS

 and

    high levels of total NKT, iNKT cells and CD8(+) iNKT subsets
    BIOCHEMICAL

 were also observed when compared to the healthy control and

    GD
    DIAGNOSIS

 patient

    without lupus nephritis
    NEG_FINDINGS

.

    Treg subset and CD8(+) iNKT abnormalities
    BIOCHEMICAL

 might be involved in

    severe lupus nephritis
    DIAGNOSIS

 in a

    GD
    DIAGNOSIS

 patient. We conclude by emphasizing the importance of the

    immunological evaluation
    PARACLINICAL

 on early diagnosis of

    autoimmunity
    DIAGNOSIS

 contributing to reduce mortality and morbidity of these patients.

Gaucher Disease (GD)
GD
lysosomal storage diseases
autoimmune disorders
malignancy
GD
lupus nephritis
GD
severe lupus nephritis
GD
autoimmunity

rare autosomal recessive disorder
Absence ofCD4(+)CD25(high)Foxp3(+) Treg


Gaucher Disease Type 2 Presenting with Collodion Membrane and Blueberry Muffin Lesions.

Collodion membrane is most closely associated with forms of autosomal recessive congenital ichthyosis, but the differential diagnosis includes many other less common etiologies. Herein we present a case of Gaucher disease (GD) type 2 in a neonate presenting with collodion membrane in addition to blueberry muffin lesions. The clinical presentation and etiology of GD and the differential diagnoses for collodion membrane and blueberry muffin lesions are briefly reviewed.

    Collodion membrane
    SYMPTOMS

 is most closely associated with forms of

    autosomal recessive congenital ichthyosis
    DIAGNOSIS

, but the

    differential diagnosis
    PARACLINICAL

 includes many other less common etiologies. Herein we present a case of

    Gaucher disease (GD) type 2
    DIAGNOSIS

 in a

    neonate
    AGE

 presenting with

    collodion membrane in addition to blueberry muffin lesions
    SYMPTOMS

. The clinical presentation and etiology of

    GD
    DIAGNOSIS

 and the

    differential diagnoses
    PARACLINICAL

 for

    collodion membrane and blueberry muffin lesions
    SYMPTOMS

 are briefly reviewed.


Pleural tuberculosis in a patient with untreated type 1 Gaucher disease.

Gaucher disease (GD) is an autosomal recessive glycolipid storage disorder, due to deficiency of the lysosomal enzyme glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. Patients with GD have alteration in their immune system and impaired microbicidal capacity of mononuclear phagocytes. It has also been demonstrated that monocyte dysfunction may correlate with the plasma glucocerebrosidase concentrations. Tuberculosis (TB) is a major public health problem in developing countries. Pleural TB is one of the most common forms of extra-pulmonary TB. Since immune system can be impaired due to the deficiency of glucocerebrosidase in various ways, TB can be observed in patients with GD especially when left untreated. Cytopenia(s) is also general finding in untreated Gaucher patients, and they may be observed most frequently due to the infiltration of the bone marrow with Gaucher cells together with the additional factor of splenomegaly. We herein present a case of an adult patient with heterozygous untreated GD1, who developed pleural TB complicated by ipsilateral pulmonary fibrosis. Before his admission to our clinic, pleurectomy operation was performed and 4-drug combination anti-TB therapy was initiated including isoniazid, rifampicin, ethambutol and pyrazinamide. Fever complaint was disappeared with anti-TB treatment but he also had fatigue and pain. After initiation of enzyme replacement therapy in addition to anti-TB treatment, clinical and hematological improvement was observed. To our knowledge, this is the first reported case of GD1 with pleural TB.

    Gaucher disease (GD)
    DIAGNOSIS

 is an

    autosomal recessive
    GENETICS

    glycolipid storage disorder
    DIAGNOSIS

, due to

    deficiency of the lysosomal enzyme glucocerebrosidase
    BIOCHEMICAL

, leading to

    accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system
    MICROSCOPIC

. Patients with

    GD
    DIAGNOSIS

 have

    alteration in their immune system
    BIOCHEMICAL

 and

    impaired microbicidal capacity of mononuclear phagocytes
    BIOCHEMICAL

. It has also been demonstrated that

    monocyte dysfunction
    BIOCHEMICAL

 may correlate with the

    plasma glucocerebrosidase concentrations
    BIOCHEMICAL

.

    Tuberculosis (TB)
    DIAGNOSIS

 is a major public health problem in developing countries.

    Pleural TB
    DIAGNOSIS

 is one of the most common forms of

    extra-pulmonary TB
    DIAGNOSIS

. Since

    immune system
    BIOCHEMICAL

 can be impaired due to the

    deficiency of glucocerebrosidase
    BIOCHEMICAL

 in various ways,

    TB
    DIAGNOSIS

 can be observed in patients with

    GD
    DIAGNOSIS

 especially when left untreated.

    Cytopenia(s)
    BIOCHEMICAL

 is also general finding in untreated

    Gaucher
    DIAGNOSIS

 patients, and they may be observed most frequently due to the

    infiltration of the bone marrow with Gaucher cells
    MICROSCOPIC

 together with the additional factor of

    splenomegaly
    SYMPTOMS

. We herein present a case of an

    adult
    AGE

 patient with

    heterozygous untreated GD1
    GENETICS

, who developed

    pleural TB
    DIAGNOSIS

 complicated by

    ipsilateral pulmonary fibrosis
    SYMPTOMS

. Before

    his
    GENDER

 admission to our clinic,

    pleurectomy operation
    MEDICATION

 was performed and

    4-drug combination anti-TB therapy was initiated including isoniazid, rifampicin, ethambutol and pyrazinamide
    MEDICATION

.

    Fever complaint was disappeared
    SYMPTOMS

 with

    anti-TB treatment
    MEDICATION

 but

    he
    GENDER

 also had

    fatigue
    SYMPTOMS

 and

    pain
    SYMPTOMS

. After

    initiation of enzyme replacement therapy in addition to anti-TB treatment
    MEDICATION

,

    clinical and hematological improvement
    SYMPTOMS

 was observed. To our knowledge, this is the first reported case of

    GD1
    DIAGNOSIS

 with

    pleural TB
    DIAGNOSIS

.

Gaucher disease (GD)
glycolipid storage disorder
GD
Tuberculosis (TB)
Pleural TB
extra-pulmonary TB
TB
GD
Gaucher
pleural TB
GD1
pleural TB

autosomal recessive
heterozygous untreated GD1

splenomegaly
ipsilateral pulmonary fibrosis
Fever complaint was disappeared
fatigue
pain
clinical and hematological improvement


[Splenomegaly and failure to thrive as a result of Gaucher disease].

Gaucher disease (GD) is the most common lysosomal storage disease with a prevalence of 1:75,000. The disease is caused by a defiency of the lysosomal enzyme glucocerebrosidase which leads to an accumulation of the substrate glycosylceramide within macrophages. GD presents with a wide spectrum of symptoms but involvement of the bones, bone marrow and spleen or liver is seen in the majority of patients. We present the case of a ten-year-old girl with massive splenomegaly, cytopenia, poor growth, learning difficulties and extreme fatigue for several years.

    Gaucher disease (GD)
    DIAGNOSIS

 is the most common

    lysosomal storage disease
    DIAGNOSIS

 with a prevalence of 1:75,000. The disease is caused by a

    defiency of the lysosomal enzyme glucocerebrosidase
    BIOCHEMICAL

 which leads to an

    accumulation of the substrate glycosylceramide within macrophages
    MICROSCOPIC

.

    GD
    DIAGNOSIS

 presents with a wide spectrum of symptoms but

    involvement of the bones, bone marrow and spleen or liver
    SYMPTOMS

 is seen in the majority of patients. We present the case of a

    ten-year-old
    AGE

    girl
    GENDER

 with

    massive splenomegaly
    SYMPTOMS

,

    cytopenia
    BIOCHEMICAL

,

    poor growth
    SYMPTOMS

,

    learning difficulties
    SYMPTOMS

 and

    extreme fatigue for several years
    SYMPTOMS

.

Gaucher disease (GD)
lysosomal storage disease
GD


Synchronous Hepatoblastoma, Neuroblastoma, and Cutaneous Capillary Hemangiomas: A Case Report.

Multiple synchronous tumors presenting in infancy raise concern for inherited or sporadic cancer predisposition syndromes, which include Beckwith-Wiedemann syndrome, familial adenomatous polyposis syndrome, and Li-Fraumeni syndrome. We report a case of a 7-month-old previously healthy male born following an in vitro fertilization-assisted twin pregnancy who presented with new-onset refractory shock, severe acidosis, and rapid decline over several hours. An autopsy revealed a ruptured liver involved by hepatoblastoma, an adrenal gland involved by neuroblastoma, and multiple cutaneous capillary hemangiomas. Standard genetic testing demonstrated that both twins were Gaucher disease (GD) carriers without evidence of other known cancer predisposition syndromes. This report describes a unique association of multiple synchronous tumors, which underscores the utility and importance of the pediatric autopsy. Moreover, given that the reported child was a GD carrier, the possibility the tumors were the result of a GD-mediated cancer-associated phenotype or an unrecognized sporadic clinical syndrome remains an unanswered, but intriguing, question worthy of further investigation.

    Multiple synchronous tumors
    SYMPTOMS

 presenting in

    infancy
    AGE

 raise concern for

    inherited
    GENETICS

 or

    sporadic cancer predisposition syndromes
    DIAGNOSIS

, which include

    Beckwith-Wiedemann syndrome
    DIAGNOSIS

,

    familial adenomatous polyposis syndrome
    DIAGNOSIS

, and

    Li-Fraumeni syndrome
    DIAGNOSIS

. We report a case of a

    7-month-old
    AGE

 previously healthy

    male
    GENDER

 born

    following an in vitro fertilization-assisted twin pregnancy
    MEDICATION

 who presented with

    new-onset refractory shock
    SYMPTOMS

,

    severe acidosis
    BIOCHEMICAL

, and

    rapid decline over several hours
    SYMPTOMS

. An

    autopsy
    PARACLINICAL

 revealed a

    ruptured liver involved by hepatoblastoma
    SYMPTOMS

,

    an adrenal gland involved by neuroblastoma
    SYMPTOMS

, and

    multiple cutaneous capillary hemangiomas
    SYMPTOMS

.

    Standard genetic testing
    PARACLINICAL

 demonstrated

    that both twins were Gaucher disease (GD) carriers
    FAMILY

    without evidence of other known cancer predisposition syndromes
    NEG_FINDINGS

. This report describes a unique

    association of multiple synchronous tumors
    SYMPTOMS

, which underscores the utility and importance of the

    pediatric autopsy
    PARACLINICAL

. Moreover, given that the reported

    child
    AGE

    was a GD carrier
    FAMILY

, the possibility the tumors were the result of a

    GD-mediated cancer-associated
    DIAGNOSIS

 phenotype or an unrecognized

    sporadic clinical syndrome
    DIAGNOSIS

 remains an unanswered, but intriguing, question worthy of further investigation.


Perinatal-lethal Gaucher disease presenting as hydrops fetalis.

Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis. We report a case of Gaucher's disease (type 2) diagnosed in a newborn who presented with Hydrops Fetalis.

    Perinatal-lethal Gaucher disease
    DIAGNOSIS

 is very rare and is considered a variant of

    type 2 Gaucher disease
    DIAGNOSIS

 that occurs in the

    neonatal
    AGE

    period
    AGE

. The most distinct features of

    perinatal-lethal Gaucher disease
    DIAGNOSIS

 are

    non-immune hydrops fetalis
    DIAGNOSIS

. Less common signs of the disease are

    hepatosplenomegaly
    SYMPTOMS

,

    ichthyosis
    SYMPTOMS

 and

    arthrogryposis
    SYMPTOMS

. We report a case of

    Gaucher's disease (type 2)
    DIAGNOSIS

 diagnosed in a

    newborn
    AGE

 who presented with

    Hydrops Fetalis
    SYMPTOMS

.

Perinatal-lethal Gaucher disease
type 2 Gaucher disease
perinatal-lethal Gaucher disease
non-immune hydrops fetalis
Gaucher's disease (type 2)

hepatosplenomegaly
ichthyosis
arthrogryposis
Hydrops Fetalis


Gaucher disease. Unusual presentation and mini-review.

We aim to describe an 8-year-old boy with an unusual clinical presentation of Gaucher disease (GD). Gaucher disease is a progressive lysosomal storage disorder due to deficiency of the specific enzyme glucocerebrosidase with varying clinical features, but often involving the monocytes-macrophages systems. This child ran a progressive course with a devastating outcome. Three distinct GD subtypes have been described with varying clinical features based on the presence or absence of neurologic involvement. Gaucher disease diagnosis is obtained via: enzyme activity assay, gene mutation study, bone marrow aspiration in addition to multiple other tests that have been successfully used in diagnosis of cases of GD. Treatment modalities include enzyme replacement treatment, substrate reduction therapy, bone marrow transplantation, blood transfusion, and surgery are available management modalities for GD. Gaucher disease is a chronic disease requiring a multidisciplinary team approach with regular follow up with multiple subspecialties.

We aim to describe an

    8-year-old
    AGE

    boy
    GENDER

 with an unusual clinical presentation of

    Gaucher disease (GD)
    DIAGNOSIS

.

    Gaucher disease
    DIAGNOSIS

 is a

    progressive lysosomal storage disorder
    DIAGNOSIS

 due to

    deficiency of the specific enzyme glucocerebrosidase
    BIOCHEMICAL

 with varying clinical features, but often involving the

    monocytes-macrophages systems
    MICROSCOPIC

. This

    child
    AGE

 ran a progressive course with a

    devastating outcome
    SYMPTOMS

. Three distinct

    GD
    DIAGNOSIS

 subtypes have been described with varying clinical features based on the presence or absence of

    neurologic involvement
    SYMPTOMS

.

    Gaucher disease
    DIAGNOSIS

 diagnosis is obtained via:

    enzyme activity assay
    PARACLINICAL

,

    gene mutation study
    PARACLINICAL

,

    bone marrow aspiration
    PARACLINICAL

 in addition to multiple other tests that have been successfully used in diagnosis of cases of

    GD
    DIAGNOSIS

. Treatment modalities include

    enzyme replacement treatment
    MEDICATION

,

    substrate reduction therapy
    MEDICATION

,

    bone marrow transplantation
    MEDICATION

,

    blood transfusion
    MEDICATION

, and

    surgery
    MEDICATION

 are available management modalities for

    GD
    DIAGNOSIS

.

    Gaucher disease
    DIAGNOSIS

 is a

    chronic disease
    DIAGNOSIS

 requiring a multidisciplinary team approach with

    regular follow up with multiple subspecialties
    PARACLINICAL

.

Gaucher disease (GD)
Gaucher disease
progressive lysosomal storage disorder
GD
Gaucher disease
GD
GD
Gaucher disease
chronic disease

devastating outcome
neurologic involvement

enzyme replacement treatment
substrate reduction therapy
bone marrow transplantation
blood transfusion
surgery


Switching from imiglucerase to miglustat for the treatment of French patients with Gaucher disease type 1: a case series.

Gaucher disease is caused by a deficiency of the enzyme β-glucocerebrosidase. Treatment with enzyme replacement therapy has been available for the past two decades but, although effective, enzyme replacement therapy can be delivered only by intravenous infusion every other week. The oral substrate reduction therapy miglustat (Zavesca®) has been available in Europe since 2002 for the treatment of patients with mild or moderate Gaucher disease type 1 for whom enzyme replacement therapy is unsuitable or not a therapeutic option. There are few published real-world data on the use of miglustat as a maintenance therapy in Gaucher disease type 1 patients switched from previous enzyme replacement therapy. We report a case series of three patients who were switched from long-term enzyme replacement therapy to miglustat for various reasons.

All three patients were Caucasian and had confirmed Gaucher disease type 1. An 80-year-old man requested a switch to oral miglustat therapy in preference to ongoing intravenous enzyme replacement therapy, a 57-year-old woman was commenced on miglustat due to a shortage of imiglucerase, and a 56-year-old woman was switched from previous enzyme replacement therapy due to allergic reactions to intravenous infusions. Hematological disease parameters were stable in each patient on previous enzyme replacement therapy. Two patients continue to be treated with miglustat, having shown good tolerability and stable core disease parameters for approximately 4 years. One patient, who was also stable during 7 years of therapy, eventually discontinued miglustat as a precaution because he developed peripheral neuropathy of as yet unknown origin.

Overall, our experience indicates that miglustat can be used as maintenance therapy for Gaucher disease type 1 after initial enzyme replacement therapy, but the selection of patients to whom this approach should be applied should be made after careful consideration of all disease parameters.

    Gaucher disease
    DIAGNOSIS

 is caused by a

    deficiency of the enzyme β-glucocerebrosidase
    BIOCHEMICAL

.

    Treatment with enzyme replacement therapy
    MEDICATION

 has been available for the past two decades but, although effective,

    enzyme replacement therapy
    MEDICATION

 can be delivered only by

    intravenous infusion every other week
    MEDICATION

. The

    oral substrate reduction therapy miglustat (Zavesca®)
    MEDICATION

 has been available in Europe since 2002 for the treatment of patients with

    mild or moderate Gaucher disease type 1
    DIAGNOSIS

 for whom

    enzyme replacement therapy is unsuitable or not a therapeutic option
    NEG_FINDINGS

. There are few published real-world data on the use of

    miglustat as a maintenance therapy
    MEDICATION

 in

    Gaucher disease type 1
    DIAGNOSIS

 patients

    switched from previous enzyme replacement therapy
    MEDICATION

. We report a case series of three patients who were

    switched from long-term enzyme replacement therapy to miglustat
    MEDICATION

 for various reasons.

All three patients were

    Caucasian
    ETHNICITY

 and had confirmed

    Gaucher disease type 1
    DIAGNOSIS

. An

    80-year-old
    AGE

    man
    GENDER

 requested a

    switch to oral miglustat therapy
    MEDICATION

 in

    preference to ongoing intravenous enzyme replacement therapy
    MEDICATION

, a

    57-year-old
    AGE

    woman
    GENDER

 was

    commenced on miglustat
    MEDICATION

 due to a

    shortage of imiglucerase
    NEG_FINDINGS

, and a

    56-year-old
    AGE

    woman
    GENDER

 was

    switched from previous enzyme replacement therapy
    MEDICATION

 due to

    allergic reactions to intravenous infusions
    NEG_FINDINGS

.

    Hematological disease parameters were stable
    SYMPTOMS

 in each patient

    on previous enzyme replacement therapy
    MEDICATION

. Two patients continue to be treated with

    miglustat
    MEDICATION

, having shown

    good tolerability
    SYMPTOMS

 and

    stable core disease parameters for approximately 4 years
    SYMPTOMS

. One patient, who was also

    stable during 7 years of therapy
    MEDICATION

, eventually

    discontinued miglustat as a precaution
    MEDICATION

 because

    he
    GENDER

 developed

    peripheral neuropathy of as yet unknown origin
    SYMPTOMS

.

Overall, our experience indicates that

    miglustat
    MEDICATION

 can be used as

    maintenance therapy
    MEDICATION

 for

    Gaucher disease type 1
    DIAGNOSIS

    after initial enzyme replacement therapy
    MEDICATION

, but the selection of patients to whom this approach should be applied should be made after careful consideration of all disease parameters.

Gaucher disease
mild or moderate Gaucher disease type 1
Gaucher disease type 1
Gaucher disease type 1
Gaucher disease type 1


Understanding the natural history of Gaucher disease.

Gaucher disease is a rare and extraordinarily heterogeneous inborn error of metabolism that exhibits diverse manifestations, a broad range of age of onset of symptoms, and a wide clinical spectrum of disease severity, from lethal disease during infancy to first age of onset of symptoms in octogenarians. Before the advent of the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the understanding of the natural history and phenotypic range of Gaucher disease was based on isolated case reports and small case series. Limited data hindered understanding of the full spectrum of the disease leading to some early misconceptions about Gaucher disease, notably, that nonneuronopathic (type 1) disease was a disease of adults only. The global scope of the ICGG Gaucher Registry, with its vast body of longitudinal data, has enabled a real appreciation of both the phenotypic spectrum of Gaucher disease and its natural history. This body of evidence represents the foundation for accurate assessment of the response to specific therapies for Gaucher disease and to the development of standard-of-care to monitor disease activity. Here, we outline the key developments in delineating the natural history of this highly complex disease and role of the ICGG Gaucher Registry in this effort.

    Gaucher disease
    DIAGNOSIS

 is a rare and extraordinarily heterogeneous

    inborn error of metabolism
    GENETICS

 that exhibits diverse manifestations, a broad range of age of onset of symptoms, and a wide clinical spectrum of disease severity, from

    lethal disease
    SYMPTOMS

 during

    infancy
    AGE

 to

    first age of onset of symptoms
    AGE

 in

    octogenarians
    AGE

. Before the advent of the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the understanding of the natural history and phenotypic range of

    Gaucher disease
    DIAGNOSIS

 was based on isolated case reports and small case series. Limited data hindered understanding of the full spectrum of the disease leading to some early misconceptions about

    Gaucher disease
    DIAGNOSIS

, notably, that

    nonneuronopathic (type 1) disease
    DIAGNOSIS

 was a disease of

    adults
    AGE

 only. The global scope of the ICGG Gaucher Registry, with its vast body of longitudinal data, has enabled a real appreciation of both the phenotypic spectrum of

    Gaucher disease
    DIAGNOSIS

 and its natural history. This body of evidence represents the foundation for accurate assessment of the response to specific therapies for

    Gaucher disease
    DIAGNOSIS

 and to the development of standard-of-care to monitor disease activity. Here, we outline the key developments in delineating the natural history of this highly complex disease and role of the ICGG Gaucher Registry in this effort.

Gaucher disease
Gaucher disease
Gaucher disease
nonneuronopathic (type 1) disease
Gaucher disease
Gaucher disease


Case Report Serious pulmonary infection in a splenectomized patient with adult type 1 Gaucher disease.

A 49-year-old man with a history of Gaucher disease type 1, resulting in serious splenomegaly and eating disorder, was referred to our department and underwent a splenectomy under general anesthesia. Gaucher disease is very rare, and its first signs are unexplained splenomegaly and hypersplenism. On preoperative examination, the patient's platelet count was slightly low, and his other test results were normal. Surprisingly, on the first postoperative day, the patient developed a lung infection. This gradually progressed to acute respiratory distress syndrome with respiratory failure, requiring intubation and mechanical ventilation. The patient eventually recovered, and he was discharged after receiving antibiotics and other treatments to enhance immunity. However, his postoperative lung infection led to a significantly prolonged and expensive hospital stay. This case suggests that we must pay close attention to the immune dysfunction of patients with Gaucher disease type 1. Anesthesia and surgery with accompanying post-traumatic stress can weaken patients' immunity and cause susceptibility to severe lung infections. Pulmonary signs and functions should be monitored closely during the perioperative period, and, if necessary, gamma globulin and thymosin should be administered early in the preoperative or postoperative period to enhance immunity.

A

    49-year-old
    AGE

    man
    GENDER

 with a history of

    Gaucher disease type 1
    DIAGNOSIS

, resulting in

    serious splenomegaly
    SYMPTOMS

 and

    eating disorder
    DIAGNOSIS

, was referred to our department and underwent a

    splenectomy under general anesthesia
    MEDICATION

.

    Gaucher disease
    DIAGNOSIS

 is very rare, and its first signs are

    unexplained splenomegaly
    BIOCHEMICAL

 and

    hypersplenism
    BIOCHEMICAL

. On preoperative examination, the patient's

    platelet count was slightly low
    BIOCHEMICAL

, and

    his
    GENDER

    other test results were normal
    NEG_FINDINGS

. Surprisingly, on the first postoperative day, the patient developed a

    lung infection
    SYMPTOMS

. This gradually progressed to

    acute respiratory distress syndrome with respiratory failure
    SYMPTOMS

, requiring

    intubation and mechanical ventilation
    MEDICATION

. The patient eventually recovered, and

    he
    GENDER

 was

    discharged
    MEDICATION

 after

    receiving antibiotics and other treatments to enhance immunity
    MEDICATION

. However, his

    postoperative lung infection
    SYMPTOMS

 led to a

    significantly prolonged and expensive hospital stay
    SYMPTOMS

. This case suggests that we must pay close attention to the

    immune dysfunction
    SYMPTOMS

 of patients with

    Gaucher disease type 1
    DIAGNOSIS

.

    Anesthesia
    MEDICATION

 and

    surgery
    MEDICATION

 with accompanying

    post-traumatic stress
    SYMPTOMS

 can

    weaken patients' immunity
    SYMPTOMS

 and cause susceptibility to

    severe lung infections
    SYMPTOMS

.

    Pulmonary signs and functions
    PARACLINICAL

 should be monitored closely during the perioperative period, and, if necessary,

    gamma globulin and thymosin
    MEDICATION

 should be administered

    early in the preoperative or postoperative period
    MEDICATION

 to

    enhance immunity
    MEDICATION

.

Gaucher disease type 1
eating disorder
Gaucher disease
Gaucher disease type 1

unexplained splenomegaly
hypersplenism
platelet count was slightly low


Type 1 and type 3 Gaucher disease in two siblings in a family: 2 unusual case reports.

Gaucher disease (GD) is an autosomal recessive disorder, characterized by lack of acid β-glucosidase (glucocerebrosidase) enzyme resulting in accumulation of glucosylceramide in different organs. It is common in Ashkenazi Jews but rare in India. Around five hundred cases are identified and diagnosed in India. We are reporting two interesting cases of type 1 non-neuropathic and type 3 juvenile subacute neuropathic variant of adult Gaucher disease in two of three siblings in a family.

    Gaucher disease (GD)
    DIAGNOSIS

 is an

    autosomal recessive disorder
    GENETICS

, characterized by

    lack of acid β-glucosidase (glucocerebrosidase) enzyme
    BIOCHEMICAL

 resulting in

    accumulation of glucosylceramide in different organs
    MICROSCOPIC

. It is common in

    Ashkenazi Jews
    ETHNICITY

 but rare in

    India
    ETHNICITY

. Around five hundred cases are identified and diagnosed in

    India
    ETHNICITY

. We are reporting two interesting cases of

    type 1 non-neuropathic and type 3 juvenile subacute neuropathic variant of adult Gaucher disease
    DIAGNOSIS

    in two of three siblings in a family
    FAMILY

.


Replacement Therapy for Gaucher Disease during Pregnancy: A Case Report.

Gaucher disease is a lysosomal storage disorder due to deficiency of glucocerebrosidase enzyme. In this study, a case of enzyme-treated woman during her pregnancy was reported.

A 27-year old woman with type I Gaucher disease was managed for pregnancy until delivery. She underwent elective splenectomy at age 26 years and was treated with 19-38 units/kg of imiglucerase. A conservative approach with close monitoring of both mother and baby was planned.

In the 39th week of pregnancy, a healthy male baby of 3180 g was delivered via cesarean section.

Apart from mild hematological complications, the pregnancy, the delivery and the puerperium were uneventful. In this case report, the issue of therapy and risk assessment in pregnancy in patients with type I Gaucher disease was discussed.

    Gaucher disease
    DIAGNOSIS

 is a

    lysosomal storage disorder
    DIAGNOSIS

 due to

    deficiency of glucocerebrosidase enzyme
    BIOCHEMICAL

. In this study, a case of

    enzyme-treated
    MEDICATION

    woman
    GENDER

 during

    her
    GENDER

    pregnancy
    MEDICATION

 was reported.

A

    27-year old
    AGE

    woman
    GENDER

 with

    type I Gaucher disease
    DIAGNOSIS

 was

    managed for pregnancy
    MEDICATION

 until

    delivery
    MEDICATION

.

    She
    GENDER

 underwent

    elective splenectomy
    MEDICATION

 at

    age 26 years
    AGE

 and was

    treated with 19-38 units/kg of imiglucerase
    MEDICATION

. A

    conservative approach
    MEDICATION

 with

    close monitoring of both mother and baby
    PARACLINICAL

 was planned.

In the

    39th week of pregnancy
    AGE

, a

    healthy male baby of 3180 g
    MEDICATION

 was delivered via

    cesarean section
    MEDICATION

.

Apart from

    mild hematological complications
    SYMPTOMS

, the

    pregnancy
    SYMPTOMS

, the delivery and the

    puerperium were uneventful
    NEG_FINDINGS

. In this case report, the issue of therapy and risk assessment in

    pregnancy
    DIAGNOSIS

 in patients with

    type I Gaucher disease
    DIAGNOSIS

 was discussed.

Gaucher disease
lysosomal storage disorder
type I Gaucher disease
pregnancy
type I Gaucher disease

mild hematological complications
pregnancy


Gaucher disease with jawbone involvement: a case report.

Gaucher disease is an autosomal recessive systemic condition, and the most common of the lysosomal storage disorders. It is characterized by lipid accumulation in certain cells and organs, particularly macrophages, which appear on light microscopy as 'Gaucher cells' or vacuolated lipid-laden reticuloendothelial cells. Long bone involvement is common in Gaucher disease, whereas craniofacial bone involvement is extremely rare. Reports confirming the diagnoses of Gaucher disease involving craniofacial bones by histopathologic evidence are even rarer.

A 46-year-old Caucasian Ashkenazi Jewish woman with Gaucher disease presented with jawbone pain and lytic radiographic lesions of her mandible. Surgical biopsy of a mandibular lesion revealed Gaucher cells infiltrating the mandible, which correlated with radiographic and clinical findings, supporting a diagnosis of Gaucher disease with jawbone involvement.

Lysosomal storage diseases can have head and neck manifestations, and bone involvement in Gaucher disease is common. Therefore, careful consideration of signs and symptoms and medical history, with a thorough review of systems, is important when evaluating patients with lysosomal storage disorders to rule out head and neck involvement of disease. Biopsy may be warranted in some cases for more definitive diagnosis of painful jawbone lesions and to rule out other odontogenic and non-odontogenic conditions in the differential diagnosis.

    Gaucher disease
    DIAGNOSIS

 is an

    autosomal recessive
    GENETICS

    systemic condition
    DIAGNOSIS

, and the most common of the

    lysosomal storage disorders
    DIAGNOSIS

. It is characterized by

    lipid accumulation in certain cells and organs, particularly macrophages, which appear
    MICROSCOPIC

 on

    light microscopy
    PARACLINICAL

    as 'Gaucher cells' or vacuolated lipid-laden reticuloendothelial cells
    MICROSCOPIC

.

    Long bone involvement
    SYMPTOMS

 is common in

    Gaucher disease
    DIAGNOSIS

, whereas

    craniofacial bone involvement
    SYMPTOMS

 is extremely rare. Reports confirming the diagnoses of

    Gaucher disease
    DIAGNOSIS

 involving

    craniofacial bones
    SYMPTOMS

 by

    histopathologic evidence
    PARACLINICAL

 are even rarer.

A

    46-year-old
    AGE

    Caucasian
    ETHNICITY

    Ashkenazi Jewish
    ETHNICITY

    woman
    GENDER

 with

    Gaucher disease
    DIAGNOSIS

 presented with

    jawbone pain
    SYMPTOMS

 and

    lytic radiographic lesions of her mandible
    SYMPTOMS

.

    Surgical biopsy of a mandibular lesion
    PARACLINICAL

 revealed

    Gaucher cells infiltrating the mandible
    MICROSCOPIC

, which correlated with radiographic and clinical findings, supporting a diagnosis of

    Gaucher disease
    DIAGNOSIS

 with

    jawbone involvement
    SYMPTOMS

.

    Lysosomal storage diseases
    DIAGNOSIS

 can have

    head and neck manifestations
    SYMPTOMS

, and

    bone involvement
    SYMPTOMS

 in

    Gaucher disease
    DIAGNOSIS

 is common. Therefore, careful consideration of signs and symptoms and medical history, with a

    thorough review of systems
    PARACLINICAL

, is important when evaluating patients with

    lysosomal storage disorders
    DIAGNOSIS

 to rule out

    head and neck involvement of disease
    SYMPTOMS

.

    Biopsy
    PARACLINICAL

 may be warranted in some cases for more definitive diagnosis of

    painful jawbone lesions
    SYMPTOMS

 and to rule out other

    odontogenic and non-odontogenic conditions
    NEG_FINDINGS

 in the

    differential diagnosis
    PARACLINICAL

.

Gaucher disease
systemic condition
lysosomal storage disorders
Gaucher disease
Gaucher disease
Gaucher disease
Gaucher disease
Lysosomal storage diseases
Gaucher disease
lysosomal storage disorders


CNS, lung, and lymph node involvement in Gaucher disease type 3 after 11 years of therapy: clinical, histopathologic, and biochemical findings.

A Caucasian male with Gaucher disease type 3, treated with continuous enzyme therapy (ET) for 11 years, experienced progressive mesenteric and retroperitoneal lymphadenopathy, lung disease, and neurological involvement leading to death at an age of 12.5 years. Autopsy showed significant pathology of the brain, lymph nodes, and lungs. Liver and spleen glucosylceramide (GluCer) and glucosylsphingosine (GluS) levels were nearly normal and storage cells were cleared. Clusters of macrophages and very elevated GluCer and GluS levels were in the lungs, and brain parenchymal and perivascular regions. Compared to normal brain GluCer (GC 18:0), GluCer species with long fatty acid acyl chains were increased in the patient's brain. This profile was similar to that in the patient's lungs, suggesting that these lipids were present in brain perivascular macrophages. In the patient's brain, generalized astrogliosis, and enhanced LC3, ubiquitin, and Tau signals were identified in the regions surrounding macrophage clusters, indicating proinflammation, altered autophagy, and neurodegeneration. These findings highlight the altered phenotypes resulting from increased longevity due to ET, as well as those in poorly accessible compartments of brain and lung, which manifested progressive disease involvement despite ET.

A

    Caucasian
    ETHNICITY

    male
    GENDER

 with

    Gaucher disease type 3
    DIAGNOSIS

,

    treated with continuous enzyme therapy (ET) for 11 years
    MEDICATION

, experienced

    progressive mesenteric and retroperitoneal lymphadenopathy
    SYMPTOMS

,

    lung disease
    SYMPTOMS

, and

    neurological involvement
    SYMPTOMS

 leading to

    death
    SYMPTOMS

 at an

    age of 12.5 years
    AGE

.

    Autopsy
    PARACLINICAL

 showed

    significant pathology of the brain, lymph nodes, and lungs
    MICROSCOPIC

.

    Liver and spleen glucosylceramide (GluCer) and glucosylsphingosine (GluS) levels were nearly normal
    NEG_FINDINGS

 and

    storage cells were cleared
    MICROSCOPIC

.

    Clusters of macrophages and very elevated GluCer and GluS levels were in the lungs, and brain parenchymal and perivascular regions
    MICROSCOPIC

. Compared to

    normal brain GluCer (GC 18:0), GluCer species with long fatty acid acyl chains were increased in the patient's brain
    MICROSCOPIC

. This

    profile was similar to that in the patient's lungs
    MICROSCOPIC

, suggesting that

    these lipids were present in brain perivascular macrophages
    MICROSCOPIC

. In the patient's brain,

    generalized astrogliosis
    MICROSCOPIC

, and

    enhanced LC3, ubiquitin, and Tau signals were identified in the regions surrounding macrophage clusters
    MICROSCOPIC

, indicating

    proinflammation
    MICROSCOPIC

,

    altered autophagy
    MICROSCOPIC

, and

    neurodegeneration
    SYMPTOMS

. These findings highlight the altered phenotypes resulting from increased longevity due to

    ET
    MEDICATION

, as well as those in

    poorly accessible compartments of brain and lung
    MICROSCOPIC

, which manifested

    progressive disease involvement
    SYMPTOMS

    despite ET
    NEG_FINDINGS

.


Imatinib as rescue therapy in a patient with pulmonary hypertension associated with Gaucher disease.

Pulmonary hypertension (PH) is a known complication of Gaucher disease (GD) and splenectomy. Although it resembles World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH), PH due to GD or splenectomy is part of WHO group 5. There are no clinical trials testing therapies in PH due to GD or splenectomy. Several reports suggest that PAH-specific therapies are beneficial in patients with PH due to GD, although data are insufficient to formulate a treatment algorithm for these patients. The tyrosine kinase inhibitor imatinib has been investigated in the treatment of severe PAH, but not in PH WHO group 5. We report a patient with GD and splenectomy who developed PH that progressed while on conventional PAH-specific therapy and improved once imatinib was added to her treatment regimen. This is the first report, to our knowledge, describing significant subjective and objective improvements in response to imatinib in a patient with WHO group 5 PH.

    Pulmonary hypertension (PH)
    DIAGNOSIS

 is a known complication of

    Gaucher disease (GD)
    DIAGNOSIS

 and

    splenectomy
    MEDICATION

. Although it resembles World Health Organization (WHO

    ) group 1 pulmonary arterial hypertension (PAH)
    DIAGNOSIS

,

    PH
    DIAGNOSIS

 due to

    GD
    DIAGNOSIS

 or

    splenectomy
    MEDICATION

 is part of WHO group 5. There are no clinical trials testing therapies in

    PH
    DIAGNOSIS

 due to

    GD
    DIAGNOSIS

 or

    splenectomy
    MEDICATION

. Several reports suggest that

    PAH-specific therapies
    MEDICATION

 are beneficial in patients with

    PH due to GD
    DIAGNOSIS

, although data are insufficient to formulate a treatment algorithm for these patients. The

    tyrosine kinase inhibitor imatinib
    MEDICATION

 has been investigated in the treatment of

    severe PAH
    DIAGNOSIS

, but not in

    PH WHO group 5
    DIAGNOSIS

. We report a patient with

    GD
    DIAGNOSIS

 and

    splenectomy
    MEDICATION

 who developed

    PH
    SYMPTOMS

 that progressed

    while on conventional PAH-specific therapy
    NEG_FINDINGS

 and improved once

    imatinib was added to her treatment regimen
    MEDICATION

. This is the first report, to our knowledge, describing

    significant subjective and objective improvements in response
    SYMPTOMS

 to

    imatinib
    MEDICATION

 in a patient with

    WHO group 5 PH
    DIAGNOSIS

.


Arylsulphatase A activity in familial parkinsonism: a pathogenetic role?

Cellular mechanism leading to Parkinson Disease (PD) is still unknown, but impairment of lysosomal degradation of aberrant proteins seems to play a crucial role. The most known lysosomal disease associated with PD is Gaucher Disease. However, actually a number of different lysosomal disorders have been linked with PD. We report three families with Arylsulphatase A partial deficit in which we can find a high recurrence of parkinsonism among the siblings. The pedigree members show as well some atypical signs and symptoms among the PD spectrum features. Arylsulphatase A plays a crucial role in protein degradation. Even if a possibly casual association cannot be excluded, it can be speculated that Arylsulphatase A partial deficit can act as a cofactor for neurodegeneration in subjects with other genetic or environmental predispositions to PD or to other neurodegenerative disease.

Cellular mechanism leading to

    Parkinson Disease (PD)
    DIAGNOSIS

 is still unknown, but

    impairment of lysosomal degradation of aberrant proteins
    BIOCHEMICAL

 seems to play a crucial role. The most known

    lysosomal disease
    DIAGNOSIS

 associated with

    PD
    DIAGNOSIS

 is

    Gaucher Disease
    DIAGNOSIS

. However, actually a number of different

    lysosomal disorders
    DIAGNOSIS

 have been linked with

    PD
    DIAGNOSIS

. We report three families with

    Arylsulphatase A partial deficit
    BIOCHEMICAL

 in which we can find

    a high recurrence of parkinsonism among the siblings
    FAMILY

. The

    pedigree members
    FAMILY

 show as well some

    atypical signs and symptoms among the PD spectrum features
    SYMPTOMS

.

    Arylsulphatase A
    BIOCHEMICAL

 plays a crucial role in

    protein degradation
    BIOCHEMICAL

. Even if a possibly casual association cannot be excluded, it can be speculated that

    Arylsulphatase A partial deficit
    BIOCHEMICAL

 can act as a cofactor for

    neurodegeneration
    SYMPTOMS

 in subjects with other

    genetic or environmental predispositions to PD
    FAMILY

 or to other

    neurodegenerative disease
    DIAGNOSIS

.

Parkinson Disease (PD)
lysosomal disease
PD
Gaucher Disease
lysosomal disorders
PD
neurodegenerative disease


Haemorrhagic pericardial effusion in type I Gaucher's disease.

Gaucher's disease is a rare lysosomal storage disorder. Excess accumulation of glucosylceramide predominantly occurs in abdominal viscera. Cardiac involvement is rare, though they generally represent as restrictive cardiomyopathy and pericarditis. Our case, a 19-year old boy initially presented with hepatosplenomegaly but later diagnosed with haemorrhagic pericardial effusion. Enzyme supplementation gives successful outcome but our case was managed symptomatically with pericardiocentesis.

    Gaucher's disease
    DIAGNOSIS

 is a

    rare lysosomal storage disorder
    DIAGNOSIS

.

    Excess accumulation of glucosylceramide
    MICROSCOPIC

 predominantly occurs

    in abdominal viscera
    MICROSCOPIC

.

    Cardiac involvement
    SYMPTOMS

 is rare, though they generally represent as

    restrictive cardiomyopathy
    SYMPTOMS

 and

    pericarditis
    DIAGNOSIS

. Our case, a

    19-year old
    AGE

    boy
    GENDER

 initially presented with

    hepatosplenomegaly
    SYMPTOMS

 but later diagnosed with

    haemorrhagic pericardial effusion
    SYMPTOMS

.

    Enzyme supplementation
    MEDICATION

 gives successful outcome but our case was

    managed symptomatically
    MEDICATION

 with

    pericardiocentesis
    MEDICATION

.

Gaucher's disease
rare lysosomal storage disorder
pericarditis

Cardiac involvement
restrictive cardiomyopathy
hepatosplenomegaly
haemorrhagic pericardial effusion

Enzyme supplementation
managed symptomatically
pericardiocentesis


Extraosseous Gaucher cell deposition without adjacent bone involvement.

Extraosseous Gaucher cell deposits are a rare complication of Gaucher disease that can mimic malignancy. We describe a case of Gaucher cell deposition in the subcutaneous soft tissues overlying the lower thoracic spine in an 18-year-old woman with known type III Gaucher disease. This case is unique in the literature because this subcutaneous Gaucher mass was not associated with extension from underlying bone involvement or clear lymph node origin. It demonstrated no discernible continuity with the adjacent thoracic spinous processes, the cortices of which appeared intact. Although patients with Gaucher disease are at increased risk of malignancy, Gaucher cell deposition should remain a differential consideration for soft tissue masses with or without adjacent bone involvement in patients with known Gaucher disease.

    Extraosseous Gaucher cell deposits
    MICROSCOPIC

 are a rare complication of

    Gaucher disease
    DIAGNOSIS

 that can mimic

    malignancy
    DIAGNOSIS

. We describe a case of

    Gaucher cell deposition in the subcutaneous soft tissues overlying the lower thoracic spine
    MICROSCOPIC

 in an

    18-year-old
    AGE

    woman
    GENDER

 with known

    type III Gaucher disease
    DIAGNOSIS

. This case is unique in the literature because this

    subcutaneous Gaucher mass
    MICROSCOPIC

 was

    not associated with extension from underlying bone involvement or clear lymph node origin
    NEG_FINDINGS

. It demonstrated

    no discernible continuity with the adjacent thoracic spinous processes, the cortices of which appeared intact
    NEG_FINDINGS

. Although patients with

    Gaucher disease
    DIAGNOSIS

 are at increased risk of

    malignancy
    DIAGNOSIS

,

    Gaucher cell deposition
    MICROSCOPIC

 should remain a differential consideration for

    soft tissue masses
    SYMPTOMS

    with or without adjacent bone involvement
    SYMPTOMS

 in patients with known

    Gaucher disease
    DIAGNOSIS

.

Gaucher disease
malignancy
type III Gaucher disease
Gaucher disease
malignancy
Gaucher disease


Heterogeneous pattern of bone disease in adult type 1 Gaucher disease: clinical and pathological correlates.

Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach.

    Gaucher disease (GD)
    DIAGNOSIS

 is a

    lysosomal storage disorder
    DIAGNOSIS

 characterized by

    accumulation of glucosylceramide in macrophages, so-called Gaucher cells
    MICROSCOPIC

, as a result of a

    deficiency of the lysosomal enzyme glucocerebrosidase
    BIOCHEMICAL

.

    Bone complications
    SYMPTOMS

 are an important cause of morbidity of

    GD
    DIAGNOSIS

 and are thought to result from

    imbalance in bone remodeling
    SYMPTOMS

.

    Bone manifestations
    SYMPTOMS

 among

    GD
    DIAGNOSIS

 patients demonstrate a large variation including

    increased osteoclastic bone resorption
    SYMPTOMS

,

    low bone formation
    SYMPTOMS

 and

    osteonecrosis
    SYMPTOMS

. The purpose of the current case series is to describe the histological features observed in

    undecalcified bone samples
    PARACLINICAL

, obtained from three

    GD
    DIAGNOSIS

 patients, and evaluate the relationship with clinical features in these patients.

    Bone fragments
    PARACLINICAL

 were obtained from three

    adult
    AGE

    type 1 GD
    DIAGNOSIS

 patients with variable degrees

    of bone disease
    SYMPTOMS

 during

    orthopedic surgery
    MEDICATION

. Specimens were

    embedded without prior decalcification in methylmethacrylate
    MEDICATION

 and

    prepared for histology
    PARACLINICAL

 according to standardized laboratory procedures.

    Histology
    PARACLINICAL

 revealed a

    heterogeneous pattern of bone involvement
    SYMPTOMS

.

    High cellularity of bone marrow
    MICROSCOPIC

,

    abundant presence of Gaucher cells (GCs) and high turnover
    MICROSCOPIC

 were observed in a patient with a

    history of multiple bone complications
    SYMPTOMS

, while

    minimal bone turnover
    NEG_FINDINGS

 and

    few GCs
    MICROSCOPIC

 were detected in the mildest affected patient in this series. An intermediate picture with

    relatively low bone turnover
    SYMPTOMS

 and a

    substantial amount of Gaucher cells
    MICROSCOPIC

 was demonstrated in the third, moderately affected patient.

    No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted
    NEG_FINDINGS

.

    Plastic embedding
    PARACLINICAL

 and subsequent

    Goldner and TRAP staining
    PARACLINICAL

 offered a unique possibility to study bone histological findings in

    GD
    DIAGNOSIS

. Our data show that

    bone manifestations
    SYMPTOMS

 in

    GD
    DIAGNOSIS

 may vary both clinically as well as histologically and

    bone disease
    DIAGNOSIS

 in

    GD
    DIAGNOSIS

 will likely require a personalized approach.

Gaucher disease (GD)
lysosomal storage disorder
GD
GD
GD
type 1 GD
GD
GD
bone disease
GD


Painless transient bone marrow edema syndrome in a pediatric patient.

Transient regional migratory osteoporosis, considered to be part of the spectrum of bone marrow edema syndrome, is a rare condition with an unknown etiology. Patients usually present with lower extremity pain, most commonly in the 4th-5th decades of life. We describe a 15-year-old male patient with type 1 Gaucher disease who presented with transient bone marrow edema syndrome with features most closely resembling regional migratory osteoporosis. The patient presented with bone marrow edema of the lateral tibial epiphysis of his right knee that was incidentally seen on routine surveillance MRI that was performed as protocol for patients with type 1 Gaucher disease on enzyme replacement therapy. At this time, the patient had no pain and physical examination was normal. Follow-up MRI of the right knee 4 months afterward showed complete resolution of the signal abnormality in the right tibial epiphysis, and repeat study 8 months later displayed a new focus of painless migratory edema of the medial tibial epiphysis of the same knee. These changes completely resolved as well. Marrow signal abnormalities in children with Gaucher disease can have a broad differential, including infection, marrow infiltration, trauma, osteonecrosis, and bone marrow edema syndrome, amongst others. Correct diagnosis of bone marrow edema syndrome is critical, as this disease process most often resolves on conservative measures. The unusual presentation of transient bone marrow edema syndrome with regional migratory osteoporosis features in a young patient with Gaucher disease is described.

    Transient regional migratory osteoporosis
    SYMPTOMS

, considered to be part of the spectrum of

    bone marrow edema syndrome
    DIAGNOSIS

, is a rare condition with an unknown etiology. Patients usually present with

    lower extremity pain
    SYMPTOMS

, most commonly in the

    4th-5th decades of life
    AGE

. We describe a

    15-year-old
    AGE

    male
    GENDER

 patient with

    type 1 Gaucher disease
    DIAGNOSIS

 who presented with

    transient bone marrow edema syndrome
    SYMPTOMS

 with

    features most closely resembling regional migratory osteoporosis
    SYMPTOMS

. The patient presented with

    bone marrow edema of the lateral tibial epiphysis of his right knee
    SYMPTOMS

 that was incidentally seen on routine

    surveillance MRI
    PARACLINICAL

 that was performed as protocol for patients with

    type 1 Gaucher disease
    DIAGNOSIS

 on

    enzyme replacement therapy
    MEDICATION

. At this time, the patient had

    no pain
    NEG_FINDINGS

 and

    physical examination was normal
    NEG_FINDINGS

.

    Follow-up MRI of the right knee
    PARACLINICAL

 4 months afterward showed

    complete resolution of the signal abnormality in the right tibial epiphysis
    SYMPTOMS

, and repeat study 8 months later displayed a

    new focus of painless migratory edema of the medial tibial epiphysis of the same knee
    SYMPTOMS

.

    These changes completely resolved
    SYMPTOMS

 as well.

    Marrow signal abnormalities
    SYMPTOMS

 in

    children
    AGE

 with

    Gaucher disease
    DIAGNOSIS

 can have a broad differential, including

    infection
    DIAGNOSIS

,

    marrow infiltration
    SYMPTOMS

,

    trauma
    SYMPTOMS

,

    osteonecrosis
    DIAGNOSIS

, and

    bone marrow edema syndrome
    DIAGNOSIS

, amongst others. Correct diagnosis of

    bone marrow edema syndrome
    DIAGNOSIS

 is critical, as this disease process most often resolves on

    conservative measures
    MEDICATION

. The unusual presentation of

    transient bone marrow edema syndrome with regional migratory osteoporosis features
    SYMPTOMS

 in a

    young
    AGE

 patient with

    Gaucher disease
    DIAGNOSIS

 is described.

bone marrow edema syndrome
type 1 Gaucher disease
type 1 Gaucher disease
Gaucher disease
infection
osteonecrosis
bone marrow edema syndrome
bone marrow edema syndrome
Gaucher disease

enzyme replacement therapy
conservative measures


Niemann-Pick disease type C or Gaucher's disease type 3? A clinical conundrum.

We describe a patient who presented with a neurovisceral syndrome characterised by ataxia, bulbar dysfunction, supranuclear gaze palsy, splenomegaly and foamy histiocytes in the bone marrow. This presentation was suggestive of a lysosomal storage disorder such as Niemann-Pick disease type C or Gaucher's disease type 3. We review the presentation of these disorders, with a focus on the neurological features. In addition, we briefly discuss the disease-modifying therapeutic options which have recently become available.

We describe a patient who presented with a

    neurovisceral syndrome
    DIAGNOSIS

 characterised by

    ataxia
    SYMPTOMS

,

    bulbar dysfunction
    SYMPTOMS

,

    supranuclear gaze palsy
    SYMPTOMS

,

    splenomegaly
    SYMPTOMS

 and

    foamy histiocytes in the bone marrow
    MICROSCOPIC

. This presentation was suggestive of a

    lysosomal storage disorder
    DIAGNOSIS

 such as

    Niemann-Pick disease type C
    DIAGNOSIS

 or

    Gaucher's disease type 3
    DIAGNOSIS

. We review the presentation of these disorders, with a focus on the neurological features. In addition, we briefly discuss the

    disease-modifying
    MEDICATION

 therapeutic options which have recently become available.

neurovisceral syndrome
lysosomal storage disorder
Niemann-Pick disease type C
Gaucher's disease type 3

ataxia
bulbar dysfunction
supranuclear gaze palsy
splenomegaly


Congenital dyserythropoietic anemia, type II with SEC23B exon 12 c.1385 A → G mutation, and pseudo-Gaucher cells in two siblings.

Congenital dyserythropoietic anemia (CDA) represents a genotypically and phenotypically heterogeneous group of disorders. CDA type II, the most frequent variant, was recently shown to be caused by mutations in the gene encoding the secretory COPII component SEC23B. We report two siblings hailing from Punjab in northern India with classical CDA type II where this mutation was demonstrated.

A 7-year-old girl presented with transfusion-dependent anemia, splenomegaly, and progressive growth failure since 1 year of age. Her 5-year-old brother was similarly afflicted, but there was no other family history. Extensive prior work-up for hemolytic anemia, storage and metabolic disorders, and infectious diseases was negative. Hemoglobin was 71 g/l with normal leukocyte, platelet, and corrected reticulocyte counts. Bone marrow examination revealed marked normoblastic erythroid hyperplasia with dyserythropoiesis (36%) and the presence of bi- and multinucleated erythroblasts with equal-sized nuclei. Many pseudo-Gaucher cells were also seen. Iron stores were increased although ring sideroblasts were absent. Hereditary erythrocyte multinuclearity with positive acidified serum (HEMPAS) test revealed lysis of the red cells in four out of five control sera.

Genomic DNA sequencing of the SEC23B exon 12 revealed homozygosity for c.1385 A → G; Y462C mutations in both siblings.

CDA has traditionally been a difficult diagnosis to establish, since it requires exclusion of other causes of dyserythropoiesis and the performance of complex tests including HEMPAS and electron microscopy for confirmation. The availability of molecular genetic testing for SEC23B promises to streamline and hasten the diagnostic process for this rare and intriguing disease.

    Congenital dyserythropoietic anemia (CDA)
    DIAGNOSIS

 represents a genotypically and phenotypically heterogeneous group of disorders.

    CDA type II
    DIAGNOSIS

, the most frequent variant, was recently shown to be caused by mutations in the gene encoding the secretory COPII component SEC23B. We report two

    siblings hailing
    FAMILY

 from

    Punjab
    ETHNICITY

 in

    northern India
    ETHNICITY

    with classical CDA type II
    FAMILY

 where this mutation was demonstrated.

A

    7-year-old
    AGE

    girl
    GENDER

 presented with

    transfusion-dependent anemia
    BIOCHEMICAL

,

    splenomegaly
    SYMPTOMS

, and

    progressive growth failure
    SYMPTOMS

    since 1 year of age
    AGE

.

    Her
    GENDER

    5-year-old brother was similarly afflicted
    AGE

, but there was

    no other family history
    NEG_FINDINGS

.

    Extensive prior work-up for hemolytic anemia
    NEG_FINDINGS

,

    storage and metabolic disorders
    DIAGNOSIS

, and

    infectious diseases was negative
    NEG_FINDINGS

.

    Hemoglobin was 71 g/l
    BIOCHEMICAL

 with

    normal leukocyte, platelet, and corrected reticulocyte counts
    NEG_FINDINGS

.

    Bone marrow examination
    PARACLINICAL

 revealed

    marked normoblastic erythroid hyperplasia with dyserythropoiesis (36%)
    MICROSCOPIC

 and the

    presence of bi- and multinucleated erythroblasts with equal-sized nuclei
    MICROSCOPIC

.

    Many pseudo-Gaucher cells were also seen
    MICROSCOPIC

.

    Iron stores were increased
    MICROSCOPIC

 although

    ring sideroblasts were absent
    NEG_FINDINGS

.

    Hereditary erythrocyte multinuclearity with positive acidified serum (HEMPAS) test
    MICROSCOPIC

 revealed

    lysis of the red cells in four out of five control sera
    MICROSCOPIC

.

    Genomic DNA sequencing of the SEC23B exon 12
    PARACLINICAL

 revealed

    homozygosity for c.1385 A → G; Y462C mutations
    GENETICS

    in both siblings
    FAMILY

.

    CDA
    DIAGNOSIS

 has traditionally been a difficult diagnosis to establish, since it requires

    exclusion of other causes of dyserythropoiesis
    NEG_FINDINGS

 and the performance of complex tests including

    HEMPAS
    PARACLINICAL

 and

    electron microscopy
    PARACLINICAL

 for confirmation. The availability of

    molecular genetic testing for SEC23B
    PARACLINICAL

 promises to streamline and hasten the diagnostic process for this rare and intriguing disease.

transfusion-dependent anemia
Hemoglobin was 71 g/l


Complex haemostatic abnormalities as a cause of bleeding after neurosurgery in a patient with Gaucher disease.

We report a treatment-naïve patient with Gaucher disease (GD) who experienced repeated bleeding after three neurosurgeries for a brain tumour, identified as an oligoastrocytoma. The patient had normal values on basic haemostatic tests: prothrombin time, 75-105%; activated partial thromboplastin time, 30.3-34 s; and mild thrombocytopaenia, 96-115 × 10(9)cells/l. However, additional tests showed mild von Willebrand factor (vWF) deficiency (vWF antigen, 56%; vWF ristocetin cofactor, 49%; factor VIII [FVIII], 54%) and abnormal collagen-mediated platelet aggregation (0.45-0.55). Bleeding control was achieved after vWF/FVIII concentrate and platelet transfusions. This case raises questions about the safe platelet count and basic haemostatic tests for assessing bleeding risk in patients with GD prior to surgery. In patients with GD, a minimum haemostatic evaluation should include platelet count and basic haemostatic tests such as fibrinogen, prothrombin time, activated partial thromboplastin time as well as platelet function tests and assessing vWF and FVIII levels. Specific coagulation factors or platelet function deficiencies should be corrected with factor concentrates or platelet transfusions.

We report a

    treatment-naïve
    NEG_FINDINGS

 patient with

    Gaucher disease (GD)
    DIAGNOSIS

 who experienced

    repeated bleeding
    SYMPTOMS

 after

    three neurosurgeries
    MEDICATION

 for a

    brain tumour
    DIAGNOSIS

, identified as an

    oligoastrocytoma
    DIAGNOSIS

. The patient had

    normal values on basic haemostatic tests: prothrombin time, 75-105%; activated partial thromboplastin time, 30.3-34 s
    NEG_FINDINGS

; and mild thrombocytopaenia, 96-115 × 10(9)cells/l. However, additional tests showed

    mild von Willebrand factor (vWF) deficiency (vWF antigen, 56%; vWF ristocetin cofactor, 49%; factor VIII [FVIII], 54%)
    BIOCHEMICAL

 and

    abnormal collagen-mediated platelet aggregation (0.45-0.55)
    BIOCHEMICAL

.

    Bleeding control
    SYMPTOMS

 was achieved after

    vWF/FVIII concentrate and platelet transfusions
    MEDICATION

. This case raises questions about the

    safe platelet count and basic haemostatic tests
    PARACLINICAL

 for assessing bleeding risk in patients with

    GD
    DIAGNOSIS

 prior to

    surgery
    MEDICATION

. In patients with

    GD
    DIAGNOSIS

, a

    minimum haemostatic evaluation
    PARACLINICAL

 should include

    platelet count and basic haemostatic tests such as fibrinogen, prothrombin time, activated partial thromboplastin time
    PARACLINICAL

 as well as

    platelet function tests
    PARACLINICAL

 and

    assessing vWF and FVIII levels
    BIOCHEMICAL

.

    Specific coagulation factors or platelet function deficiencies
    BIOCHEMICAL

 should be corrected with

    factor concentrates or platelet transfusions
    MEDICATION

.

Gaucher disease (GD)
brain tumour
oligoastrocytoma
GD
GD


Chronic neuronopathic type of Gaucher's disease with progressive myoclonic epilepsy in the absence of visceromegaly and bone involvement.

Gaucher's disease is a lysosomal storage disorder caused by the deficiency of glucocerebrosidase. Gaucher's disease has three clinical types: non-neuronopathic (Type 1), Acute Neuropathic (Type 2) and chronic neuronopathic (Type 3). The chronic neuronopathic (Type 3) is characterised by a variety of disease variants with onset in childhood with hepatomegaly, skeletal lesions and later slow horizontal saccades, treatment-resistant generalised tonic-clonic and myoclonic seizures, dementia, progressive spasticity, cognitive deterioration, ataxia and death in the second or third decade of life.

We describe a case of a 17-year-old girl who was born normally but subsequently developed treatment-refractory seizures at the age of nine with myoclonus, oculomotor apraxia, ataxia and cognitive decline. Enzyme activity of beta-glucocerebrosidase was found to be low without visceromegaly or bone involvement.

Screening for lysosomal enzyme activity should be done in patients exhibiting features suggestive of progressive myoclonic epilepsy.

    Gaucher's disease
    DIAGNOSIS

 is a

    lysosomal storage disorder
    DIAGNOSIS

 caused by the

    deficiency of glucocerebrosidase
    BIOCHEMICAL

.

    Gaucher's disease
    DIAGNOSIS

 has three clinical types:

    non-neuronopathic (Type 1)
    DIAGNOSIS

,

    Acute Neuropathic (Type 2)
    DIAGNOSIS

 and

    chronic neuronopathic (Type 3)
    DIAGNOSIS

. The

    chronic neuronopathic (Type 3)
    DIAGNOSIS

 is characterised by a variety of disease variants with onset in

    childhood
    AGE

 with

    hepatomegaly
    SYMPTOMS

,

    skeletal lesions
    SYMPTOMS

 and

    later slow horizontal saccades
    SYMPTOMS

,

    treatment-resistant generalised tonic-clonic and myoclonic seizures
    NEG_FINDINGS

,

    dementia
    SYMPTOMS

,

    progressive spasticity
    SYMPTOMS

,

    cognitive deterioration
    SYMPTOMS

,

    ataxia
    SYMPTOMS

 and

    death
    SYMPTOMS

    in the second or third decade of life
    AGE

.

We describe a case of a

    17-year-old
    AGE

    girl
    GENDER

 who was born normally but subsequently developed

    treatment-refractory seizures
    SYMPTOMS

    at the age of nine
    AGE

 with

    myoclonus
    SYMPTOMS

,

    oculomotor apraxia
    SYMPTOMS

,

    ataxia
    SYMPTOMS

 and

    cognitive decline
    SYMPTOMS

.

    Enzyme activity of beta-glucocerebrosidase was found to be low
    BIOCHEMICAL

    without visceromegaly or bone involvement
    NEG_FINDINGS

.

    Screening for lysosomal enzyme activity
    PARACLINICAL

 should be done in patients exhibiting

    features suggestive of progressive myoclonic epilepsy
    SYMPTOMS

.

Gaucher's disease
lysosomal storage disorder
Gaucher's disease
non-neuronopathic (Type 1)
Acute Neuropathic (Type 2)
chronic neuronopathic (Type 3)
chronic neuronopathic (Type 3)


Cholelithiasis in a patient with type 2 Gaucher disease.

Gaucher disease is an autosomal recessively inherited lysosomal storage disease in which a deficiency of glucocerebrosidase is associated with the accumulation of glucocerebroside in reticuloendothelial cells. Clinically, 3 types of Gaucher disease have been defined on the basis of the presence or absence of neurological symptoms. The frequency of gallbladder involvement is reportedly greater in patients with type 1 Gaucher disease than in healthy persons. We report a case of recurrent cholelithiasis and liver failure in a patient with type 2 Gaucher disease who showed severe progressive neurological involvement.

    Gaucher disease
    DIAGNOSIS

 is an

    autosomal recessively inherited
    GENETICS

    lysosomal storage disease
    DIAGNOSIS

 in which a

    deficiency of glucocerebrosidase
    BIOCHEMICAL

 is associated with the

    accumulation of glucocerebroside in reticuloendothelial cells
    MICROSCOPIC

. Clinically, 3 types of

    Gaucher disease
    DIAGNOSIS

 have been defined on the basis of the presence or absence of

    neurological symptoms
    SYMPTOMS

. The frequency of

    gallbladder involvement
    SYMPTOMS

 is reportedly greater in patients with

    type 1 Gaucher disease
    DIAGNOSIS

 than in healthy persons. We report a case of

    recurrent cholelithiasis
    SYMPTOMS

 and

    liver failure
    SYMPTOMS

 in a patient with

    type 2 Gaucher disease
    DIAGNOSIS

 who showed

    severe progressive neurological involvement
    SYMPTOMS

.

Gaucher disease
lysosomal storage disease
Gaucher disease
type 1 Gaucher disease
type 2 Gaucher disease


Oral health of a child being treated for subtype I Gaucher's disease.

Gaucher disease (GD) is an autosomal recessive disorder characterized by the absence of glucosylceramidase. The accumulation of substrates of this enzyme in the cytoplasm of cells of the phagocytary system causes skeletal and hematologic disorders, and has oral repercussions. This report describes the findings of the oral cavity of an 8-year-old diagnosed with subtype I GD who has been receiving enzyme replacement therapy for the past 6 years without interruption. The report highlights that the child had none of the most common oral disease signs and symptoms, which demonstrates the importance of early diagnosis and continuous treatment. The article also emphasizes that it is important for dentists to recognize oral manifestations of GD (in order to assist in early diagnosis) and understand how to treat the likely oral health conditions of GD patients.

    Gaucher disease (GD)
    DIAGNOSIS

 is an

    autosomal recessive disorder
    GENETICS

 characterized by the

    absence of glucosylceramidase
    BIOCHEMICAL

. The

    accumulation of substrates of this enzyme in the cytoplasm of cells of the phagocytary system
    MICROSCOPIC

 causes

    skeletal and hematologic disorders
    SYMPTOMS

, and has

    oral repercussions
    SYMPTOMS

. This report describes the findings of the oral cavity of an

    8-year-old
    AGE

 diagnosed with

    subtype I GD
    DIAGNOSIS

 who has been

    receiving enzyme replacement therapy for the past 6 years
    MEDICATION

    without interruption
    NEG_FINDINGS

. The report highlights that the

    child
    AGE

 had

    none of the most common oral disease signs and symptoms
    NEG_FINDINGS

, which demonstrates the importance of early diagnosis and

    continuous treatment
    MEDICATION

. The article also emphasizes that it is important for dentists to recognize

    oral manifestations
    SYMPTOMS

 of

    GD
    DIAGNOSIS

 (in order to assist in early diagnosis) and understand how to treat the likely oral health conditions of

    GD
    DIAGNOSIS

 patients.

skeletal and hematologic disorders
oral repercussions
oral manifestations


Gaucher's Disease, an Unusual Cause of Massive Splenomegaly, a Case Report.

Gaucher's Disease (G.D.) is an autosomal recessive disorder resulting from the accumulation of glucocerebrosidase in the cells of macrophage-monocyte system as a result of a deficiency in lysosomal glucocerebrosidase. This enzyme is encoded by a gene on chromosome-1. Here we report a case of Gaucher's Disease .G.D is rare in Yazd.

We reported a patient that presented with weakness, pallor and gradually increasing abdominal girth. Clinical examination and history pointed to be a lipid storage disease. Final diagnosis of G.D. was reported after examining the bone marrow smears. Confirmation of diagnosis on Gaucher's disease was performed by measurement of glucocerebrosidase level.

We report a case of G.D. to emphasize the importance of early recognition by clinical manifestation and histological findings. G.D. should be considered in the differential diagnosis of children with unexplained splenomegaly.

    Gaucher's Disease (G.D.)
    DIAGNOSIS

 is an

    autosomal recessive disorder
    GENETICS

 resulting from the

    accumulation of glucocerebrosidase in the cells of macrophage-monocyte system
    MICROSCOPIC

 as a result of a

    deficiency in lysosomal glucocerebrosidase
    BIOCHEMICAL

. This

    enzyme is encoded by a gene on chromosome-1
    GENETICS

. Here we report a case of

    Gaucher's Disease
    DIAGNOSIS

 .G.D is rare in

    Yazd
    ETHNICITY

.

We reported a patient that presented with

    weakness
    SYMPTOMS

,

    pallor
    SYMPTOMS

 and

    gradually increasing abdominal girth
    SYMPTOMS

.

    Clinical examination
    PARACLINICAL

 and history pointed to be a

    lipid storage disease
    DIAGNOSIS

. Final diagnosis of

    G.D.
    DIAGNOSIS

 was reported after

    examining the bone marrow smears
    PARACLINICAL

. Confirmation of diagnosis on

    Gaucher's disease
    DIAGNOSIS

 was performed by

    measurement of glucocerebrosidase level
    BIOCHEMICAL

.

We report a case of

    G.D.
    DIAGNOSIS

 to emphasize the importance of early recognition by clinical manifestation and

    histological findings
    PARACLINICAL

.

    G.D.
    DIAGNOSIS

 should be considered in the

    differential diagnosis
    PARACLINICAL

 of

    children
    AGE

 with

    unexplained splenomegaly
    SYMPTOMS

.

weakness
pallor
gradually increasing abdominal girth
unexplained splenomegaly


Focal splenic FDG uptake in a patient with Kala-Azar (visceral leishmaniasis).

We present a woman with a history of Gaucher disease and secondary portal hypertension. She went to hospital for treatment of resistant fever without apparent cause. A conventional study of fever of unknown origin did not show any pathology. For this reason, she was referred to our department for a PET/CT, which did not demonstrate a cause for the fever. Two months after, she was admitted again in hospital for fever recurrence. A new PET/CT showed FDG avid hypodense splenic lesions, suspicious for infection. Splenectomy was performed and histopathologic analysis demonstrated intracellular organisms compatible with Leishmania.

We present a

    woman
    GENDER

 with a history of

    Gaucher disease
    DIAGNOSIS

 and

    secondary portal hypertension
    SYMPTOMS

.

    She
    GENDER

 went to hospital for treatment of

    resistant fever
    SYMPTOMS

    without apparent cause
    NEG_FINDINGS

. A

    conventional study of fever of unknown origin
    NEG_FINDINGS

    did not show any pathology
    NEG_FINDINGS

. For this reason,

    she
    GENDER

 was referred to our department for a

    PET/CT
    PARACLINICAL

, which

    did not demonstrate a cause for the fever
    NEG_FINDINGS

. Two months after,

    she
    GENDER

 was admitted again in hospital for

    fever recurrence
    SYMPTOMS

. A new

    PET/CT
    PARACLINICAL

 showed

    FDG avid hypodense splenic lesions
    MICROSCOPIC

, suspicious for

    infection
    SYMPTOMS

.

    Splenectomy
    MEDICATION

 was performed and

    histopathologic analysis
    PARACLINICAL

 demonstrated

    intracellular organisms compatible with Leishmania.
    MICROSCOPIC

secondary portal hypertension
resistant fever
fever recurrence
infection


A novel SCARB2 mutation in progressive myoclonus epilepsy indicated by reduced β-glucocerebrosidase activity.

Action myoclonus renal failure (AMRF) syndrome is a rare form of progressive myoclonus epilepsy with renal dysfunction related to mutations in the SCARB2 gene. This gene is involved in lysosomal mannose-6-phosphate-independent trafficking of β-glucocerebrosidase (GC), an enzyme deficient in Gaucher disease. We report a family with myoclonic epilepsy, ataxia and skeletal muscle atrophy but without cognitive impairment or overt renal disease. A novel SCARB2 mutation was indicated by a striking discrepancy between lymphocyte and fibroblast GC activity in the proband evaluated for possible Gaucher disease. Our findings expand the genetic and phenotypic diversity of AMRF and suggest that low GC activity may present an important biochemical clue to the diagnosis of AMRF.

    Action myoclonus renal failure (AMRF) syndrome
    DIAGNOSIS

 is a rare form of

    progressive myoclonus epilepsy
    SYMPTOMS

 with

    renal dysfunction
    SYMPTOMS

 related to

    mutations in the SCARB2 gene
    GENETICS

. This gene is involved in

    lysosomal mannose-6-phosphate-independent trafficking of β-glucocerebrosidase (GC)
    BIOCHEMICAL

, an

    enzyme deficient in Gaucher disease
    BIOCHEMICAL

. We report a

    family with myoclonic epilepsy
    FAMILY

,

    ataxia
    SYMPTOMS

 and

    skeletal muscle atrophy
    SYMPTOMS

 but

    without cognitive impairment
    NEG_FINDINGS

 or

    overt renal disease
    NEG_FINDINGS

. A

    novel SCARB2 mutation
    GENETICS

 was indicated by a

    striking discrepancy between lymphocyte and fibroblast GC activity
    BIOCHEMICAL

 in the proband evaluated for possible

    Gaucher disease
    DIAGNOSIS

. Our findings expand the genetic and phenotypic diversity of

    AMRF
    DIAGNOSIS

 and suggest that

    low GC activity
    BIOCHEMICAL

 may present an important biochemical clue to the diagnosis of

    AMRF
    DIAGNOSIS

.

progressive myoclonus epilepsy
renal dysfunction
ataxia
skeletal muscle atrophy

mutations in the SCARB2 gene
novel SCARB2 mutation

without cognitive impairment
overt renal disease


Adult type 3 Gaucher disease as manifestation of R463C/Rec Nci I mutation: first reported case in the world literature.

Gaucher disease is the most common lysosomal storage disorder. It is autosomal recessive in nature and results from mutations in the GBA gene coding for acid beta glucosidase. It is classified into three types based on CNS involvement and its severity. Type 3, or chronic neuronopathic Gaucher disease, generally has an onset in childhood and by definition, includes all patients with any form of neurologic involvement who have survived the first few years of life. Here we present a 36 year old male patient presenting with hip pain showing bilateral avascular necrosis of femoral head with massive splenomegaly and on evaluation, showed mental retardation, seizures, bilateral vertical and horizontal gaze palsies and eventually turned out to be type 3b Gaucher disease. This is the first case of Type 3 Gaucher disease being reported from India with mutation analysis and only case of Type 3 Gaucher disease in world literature showing R463C/Rec Nci I mutation.

    Gaucher disease
    DIAGNOSIS

 is the most common

    lysosomal storage disorder
    DIAGNOSIS

. It is

    autosomal recessive in nature
    GENETICS

 and results from

    mutations in the GBA gene coding for acid beta glucosidase
    GENETICS

. It is classified into three types based on

    CNS involvement
    SYMPTOMS

 and its severity.

    Type 3
    DIAGNOSIS

, or

    chronic neuronopathic Gaucher disease
    DIAGNOSIS

, generally has an onset in

    childhood
    AGE

 and by definition, includes all patients with

    any form of neurologic involvement
    SYMPTOMS

 who have

    survived the first few years of life
    AGE

. Here we present a

    36 year old
    AGE

    male
    GENDER

 patient presenting with

    hip pain
    SYMPTOMS

 showing

    bilateral avascular necrosis of femoral head
    SYMPTOMS

 with

    massive splenomegaly
    SYMPTOMS

 and on evaluation, showed

    mental retardation
    SYMPTOMS

,

    seizures
    SYMPTOMS

,

    bilateral vertical and horizontal gaze palsies
    SYMPTOMS

 and eventually turned out to be

    type 3b Gaucher disease
    DIAGNOSIS

. This is the first case of

    Type 3 Gaucher disease
    DIAGNOSIS

 being reported from

    India
    ETHNICITY

 with

    mutation analysis
    PARACLINICAL

 and only case of

    Type 3 Gaucher disease
    DIAGNOSIS

 in world literature showing

    R463C/Rec Nci I mutation
    GENETICS

.

Gaucher disease
lysosomal storage disorder
Type 3
chronic neuronopathic Gaucher disease
type 3b Gaucher disease
Type 3 Gaucher disease
Type 3 Gaucher disease