Misdiagnosis of Niemann-Pick disease type C as Gaucher disease.

Niemann-Pick disease type C (NPC) is a model for inborn errors of metabolism whose gene product mediates molecular trafficking rather than catabolizing macromolecules, as in classic lipidoses. We report the case of an infant who presented with hepatosplenomegaly without neurological abnormalities. Decreased activity of acid β-glucosidase and elevated serum chitotriosidase and tartrate-resistant acid phosphatase on repeated measurements led to initial diagnosis of Gaucher disease (GD). Failure to respond to enzyme replacement therapy after one year, however, put the diagnosis in question. Cholesterol esterification assays in cultured skin fibroblasts and NPC gene analysis led to the correct diagnosis of NPC. The patient had markedly reduced cholesterol esterification and was a compound heterozygote for a known and a novel mutation in the NPC gene (395delC and 2068insTCCC), which are both predicted to lead to protein truncation. Although the full phenotype of NPC involves hepatosplenomegaly and neurodegenerative disease, the initial presentation in a pediatric patient may be restricted to visceral disease. Of interest, this patient had decreased activity of leukocyte acid β-glucosidase activity and elevated serum chitotriosidase to levels often seen in GD. Although acid β-glucosidase activity in leukocytes was low, it was in the normal range in skin fibroblasts. Therefore, diagnostic delay may occur in NPC due to false positive testing for GD. Diagnosis of NPC requires a high index of suspicion and should be considered in a patient with hepatosplenomegaly even in the absence of neurodevelopmental signs. Prompt diagnosis will become increasingly important as effective therapies are developed for NPC.

    Niemann-Pick disease type C (NPC)
    DIAGNOSIS

 is a model for

    inborn errors of metabolism
    GENETICS

 whose gene product mediates molecular trafficking rather than catabolizing macromolecules, as in classic

    lipidoses
    DIAGNOSIS

. We report the case of an

    infant
    AGE

 who presented with

    hepatosplenomegaly
    SYMPTOMS

    without neurological abnormalities
    NEG_FINDINGS

.

    Decreased activity of acid β-glucosidase
    BIOCHEMICAL

 and

    elevated serum chitotriosidase and tartrate-resistant acid phosphatase on repeated measurements
    BIOCHEMICAL

 led to initial diagnosis of

    Gaucher disease (GD)
    DIAGNOSIS

.

    Failure to respond to enzyme replacement therapy after one year
    NEG_FINDINGS

, however, put the diagnosis in question.

    Cholesterol esterification assays in cultured skin fibroblasts
    PARACLINICAL

 and

    NPC gene analysis
    PARACLINICAL

 led to the correct diagnosis of

    NPC
    DIAGNOSIS

. The patient had

    markedly reduced cholesterol esterification
    MICROSCOPIC

 and was a

    compound heterozygote for a known and a novel mutation in the NPC gene (395delC and 2068insTCCC), which are both predicted to lead to protein truncation
    GENETICS

. Although the full phenotype of

    NPC
    DIAGNOSIS

 involves

    hepatosplenomegaly
    SYMPTOMS

 and

    neurodegenerative disease
    SYMPTOMS

, the initial presentation in a

    pediatric
    AGE

 patient may be restricted to

    visceral disease
    DIAGNOSIS

. Of interest, this patient had

    decreased activity of leukocyte acid β-glucosidase activity
    BIOCHEMICAL

 and

    elevated serum chitotriosidase to levels often seen in GD
    BIOCHEMICAL

. Although

    acid β-glucosidase activity in leukocytes was low
    BIOCHEMICAL

    , it was in the normal range in skin fibroblasts
    NEG_FINDINGS

. Therefore, diagnostic delay may occur in

    NPC
    DIAGNOSIS

 due to

    false positive testing for GD
    NEG_FINDINGS

. Diagnosis of

    NPC
    DIAGNOSIS

 requires a high index of suspicion and should be considered in a patient with

    hepatosplenomegaly
    SYMPTOMS

 even in the

    absence of neurodevelopmental signs
    NEG_FINDINGS

. Prompt diagnosis will become increasingly important as effective therapies are developed for

    NPC
    DIAGNOSIS

.

Niemann-Pick disease type C (NPC)
lipidoses
Gaucher disease (GD)
NPC
NPC
visceral disease
NPC
NPC
NPC

hepatosplenomegaly
hepatosplenomegaly
neurodegenerative disease
hepatosplenomegaly


Type 2 Gaucher disease: phenotypic variation and genotypic heterogeneity.

Gaucher disease (GD), the most common lysosomal storage disease, results from a deficiency of the lysosomal enzyme glucocerebrosidase. GD has been classified into 3 types, of which type 2 (the acute neuronopathic form) is the most severe, presenting pre- or perinatally, or in the first few months of life. Traditionally, type 2 GD was considered to have the most uniform clinical phenotype when compared to other GD subtypes. However, case studies over time have demonstrated that type 2 GD, like types 1 and 3, manifests with a spectrum of phenotypes. This review includes case reports that illustrate the broad range of clinical presentations encountered in type 2 GD, as well as a discussion of associated manifestations, pathological findings, diagnostic techniques, and a review of current therapies. While type 2 GD is generally associated with severe mutations in the glucocerebrosidase gene, there is also significant genotypic heterogeneity.

    Gaucher disease (GD)
    DIAGNOSIS

, the most common

    lysosomal storage disease
    DIAGNOSIS

, results from a

    deficiency of the lysosomal enzyme glucocerebrosidase
    BIOCHEMICAL

.

    GD
    DIAGNOSIS

 has been classified into 3 types, of which

    type 2 (the acute neuronopathic form)
    DIAGNOSIS

 is the most severe, presenting

    pre- or perinatally
    AGE

, or

    in the first few months of life
    AGE

. Traditionally,

    type 2 GD
    DIAGNOSIS

 was considered to have the most uniform clinical phenotype when compared to other

    GD subtypes
    DIAGNOSIS

. However, case studies over time have demonstrated that

    type 2 GD
    DIAGNOSIS

, like

    types 1 and 3
    DIAGNOSIS

, manifests with a spectrum of phenotypes. This review includes case reports that illustrate the broad range of clinical presentations encountered in

    type 2 GD
    DIAGNOSIS

, as well as a discussion of associated manifestations, pathological findings, diagnostic techniques, and a review of current therapies. While

    type 2 GD
    DIAGNOSIS

 is generally associated with

    severe mutations in the glucocerebrosidase gene
    GENETICS

, there is also significant genotypic heterogeneity.

Gaucher disease (GD)
lysosomal storage disease
GD
type 2 (the acute neuronopathic form)
type 2 GD
GD subtypes
type 2 GD
types 1 and 3
type 2 GD
type 2 GD


Coinheritance of Gaucher disease and α-thalassemia resulting in confusion between two inherited hematologic diseases.

Gaucher type 1 disease has a wide spectrum of phenotypes ranging from asymptomatic individuals to patients with massive hepatosplenomegaly and bone involvement. In most, anemia, thrombocytopenia and splenomegaly are the primary manifestations at diagnosis, findings shared by the hemoglobinopathies. Here we report the co-inheritance of α-thalassemia and Gaucher disease in a consanguineous family followed in Iran, which resulted in confusion regarding the diagnosis. This report emphasizes the need to independently establish the diagnosis of every affected member of a family to ensure appropriate management and therapeutic decisions.

    Gaucher type 1 disease
    DIAGNOSIS

 has a wide spectrum of phenotypes ranging from

    asymptomatic
    NEG_FINDINGS

 individuals to patients with

    massive hepatosplenomegaly
    SYMPTOMS

 and

    bone involvement
    SYMPTOMS

. In most,

    anemia
    BIOCHEMICAL

,

    thrombocytopenia
    BIOCHEMICAL

 and

    splenomegaly
    SYMPTOMS

 are the primary manifestations at diagnosis, findings shared by the

    hemoglobinopathies
    DIAGNOSIS

. Here we report the

    co-inheritance of α-thalassemia and Gaucher disease
    FAMILY

 in a

    consanguineous family followed
    FAMILY

 in

    Iran
    ETHNICITY

, which resulted in confusion regarding the diagnosis. This report emphasizes the need to independently establish the diagnosis of every affected member of a family to ensure appropriate management and therapeutic decisions.

Gaucher type 1 disease
hemoglobinopathies

massive hepatosplenomegaly
bone involvement
splenomegaly


Aortic and mitral valve stenosis with regurgitation: not due to rheumatic heart disease.

The patient is a 13-year-old Mexican-American immigrant who had no previous medical care. Upon arrival to the United States she was diagnosed with severe mitral valve stenosis and regurgitation. In addition she had severe aortic stenosis with mild to moderate aortic valve regurgitation, which was thought to be rheumatic heart disease. On the basis of the clinical and echocardiographic findings she was taken to the operating room for both mitral and aortic valve replacement. Her operation was complicated by the discovery that her aorta was completely calcified, as were her coronary arteries, mitral valve and aortic valve. She underwent aortic and mitral valve replacement as well as replacement of her aortic arch. Her coronary arteries were patch augmented and reimplanted into the newly created ascending aorta. Based on the pathologic examination of the surgical tissue a diagnosis of Gaucher disease was made.

The patient is a

    13-year-old
    AGE

    Mexican-American
    ETHNICITY

    immigrant
    ETHNICITY

 who had

    no previous medical care
    NEG_FINDINGS

. Upon arrival to the United States

    she
    GENDER

 was diagnosed with

    severe mitral valve stenosis and regurgitation
    SYMPTOMS

. In addition

    she
    GENDER

 had

    severe aortic stenosis
    SYMPTOMS

 with

    mild to moderate aortic valve regurgitation
    SYMPTOMS

, which was thought to be

    rheumatic heart disease
    DIAGNOSIS

. On the basis of the clinical and echocardiographic findings

    she
    GENDER

 was taken to the operating room for

    both mitral and aortic valve replacement
    MEDICATION

.

    Her
    GENDER

 operation was complicated by the discovery that

    her aorta was completely calcified, as were her coronary arteries, mitral valve and aortic valve
    SYMPTOMS

.

    She
    GENDER

 underwent

    aortic and mitral valve replacement as well as replacement of her aortic arch
    MEDICATION

.

    Her
    GENDER

    coronary arteries were patch augmented and reimplanted into the newly created ascending aorta
    MEDICATION

. Based on the

    pathologic examination of the surgical tissue
    PARACLINICAL

 a diagnosis of

    Gaucher disease
    DIAGNOSIS

 was made.


Pulmonary hemorrhage in type 3 Gaucher disease: a case report.

A 2-year-old boy with type 3 Gaucher disease (GD) on treatment with enzyme replacement therapy (ERT) was found dead in bed having been apparently well the night before. At the time of diagnosis, he had significant respiratory symptoms (severe and persistent bouts of coughing) that had been attributed to Gaucher lung infiltration and that were controlled by inhaled and orally administered steroids. These symptoms had begun to reappear just prior to death. Postmortem revealed extensive pulmonary hemorrhage and intra-alveolar collections of Gaucher cells. There was very little evidence of GD elsewhere. Death was ascribed to pulmonary hemorrhage secondary to GD. The pathogenesis was unclear. To the best of our knowledge, this is the first case of isolated pulmonary hemorrhage secondary to GD and may represent a hitherto unrecognized complication of this condition. Given the apparent temporal relationship, we propose that it represented a severe, terminal event in the course of Gaucher lung disease.

A

    2-year-old
    AGE

    boy
    GENDER

 with

    type 3 Gaucher disease (GD)
    DIAGNOSIS

 on

    treatment with enzyme replacement therapy (ERT)
    MEDICATION

 was found

    dead in bed having been apparently well
    SYMPTOMS

 the night before. At the time of diagnosis,

    he
    GENDER

 had

    significant respiratory symptoms
    SYMPTOMS

 (

    severe and persistent bouts of coughing)
    SYMPTOMS

 that had been attributed to

    Gaucher lung infiltration
    MICROSCOPIC

 and that were controlled by

    inhaled and orally administered steroids
    MEDICATION

. These symptoms had begun to reappear just prior to

    death
    SYMPTOMS

.

    Postmortem
    PARACLINICAL

 revealed

    extensive pulmonary hemorrhage
    SYMPTOMS

 and

    intra-alveolar collections of Gaucher cells
    MICROSCOPIC

. There was very

    little evidence of GD elsewhere
    NEG_FINDINGS

.

    Death
    SYMPTOMS

 was ascribed to

    pulmonary hemorrhage secondary to GD
    SYMPTOMS

. The pathogenesis was unclear. To the best of our knowledge, this is the first case of

    isolated pulmonary hemorrhage
    SYMPTOMS

    secondary to GD
    DIAGNOSIS

 and may represent a hitherto unrecognized complication of this condition. Given the apparent temporal relationship, we propose that it represented a severe, terminal event in the course of

    Gaucher lung disease
    DIAGNOSIS

.

type 3 Gaucher disease (GD)
secondary to GD
Gaucher lung disease


Primary bone angiosarcoma in a patient with Gaucher disease.

Skeletal pain and the resulting skeletal complications are common in Gaucher disease. The patients therefore usually receive symptomatic treatment and only rarely undergo additional diagnostic procedures. The paper describes the case of a patient with Gaucher disease who had advancing pain in the right knee and femur, which was first attributed to the basic disease. After a pathological fracture of the painful part of the leg, it became evident that the patient suffered from primary bone angiosarcoma. From this case, we learnt that not every skeletal pain in Gaucher disease represents a skeletal manifestation of this disease. Further surgical treatment was made difficult by the thrombocyte dysfunction discovered in the patient.

    Skeletal pain
    SYMPTOMS

 and the resulting

    skeletal complications
    SYMPTOMS

 are common in

    Gaucher disease
    DIAGNOSIS

. The patients therefore usually receive

    symptomatic treatment
    MEDICATION

 and only rarely undergo additional diagnostic procedures. The paper describes the case of a patient with

    Gaucher disease
    DIAGNOSIS

 who had

    advancing pain in the right knee and femur
    SYMPTOMS

, which was first attributed to the basic disease. After a

    pathological fracture of the painful part of the leg
    SYMPTOMS

, it became evident that the patient suffered from

    primary bone angiosarcoma
    DIAGNOSIS

. From this case, we learnt that not every

    skeletal pain
    SYMPTOMS

 in

    Gaucher disease
    DIAGNOSIS

 represents a

    skeletal
    SYMPTOMS

 manifestation of this disease. Further

    surgical treatment
    MEDICATION

 was made difficult by the

    thrombocyte dysfunction
    BIOCHEMICAL

 discovered in the patient.

Gaucher disease
Gaucher disease
primary bone angiosarcoma
Gaucher disease

symptomatic treatment
surgical treatment


Long-term outcomes of liver transplantation in type 1 Gaucher disease.

Gaucher disease (GD) is the most prevalent lysosomal storage disorder. Enzyme replacement therapy (ERT) has demonstrable efficacy in reversing clinical and pathological manifestations of GD. We report four patients with GD and severe hepatic impairment who were successfully treated by orthotopic liver transplantation. Liver failure resulted from GD in two patients and due to a comorbidity in two others (HCV and autoimmune chronic active hepatitis). Following successful liver transplantation, patients received long-term ERT. Liver transplantation is a life-saving treatment for end-stage liver disease in patients with Gaucher disease. All four patients have had excellent outcomes from liver transplantation for up to 10 years postprocedure with no evidence of Gaucher-related pathology in the graft.

    Gaucher disease (GD)
    DIAGNOSIS

 is the most prevalent

    lysosomal storage disorder
    DIAGNOSIS

.

    Enzyme replacement therapy (ERT)
    MEDICATION

 has demonstrable efficacy in

    reversing clinical and pathological manifestations
    SYMPTOMS

 of

    GD
    DIAGNOSIS

. We report four patients with

    GD
    DIAGNOSIS

 and

    severe hepatic impairment
    SYMPTOMS

 who were successfully treated by

    orthotopic liver transplantation
    MEDICATION

.

    Liver failure
    SYMPTOMS

 resulted from

    GD
    DIAGNOSIS

 in two patients and due to a comorbidity in two others (

    HCV and autoimmune chronic active hepatitis)
    DIAGNOSIS

. Following

    successful liver transplantation
    MEDICATION

, patients received

    long-term ERT
    MEDICATION

.

    Liver transplantation
    MEDICATION

 is a

    life-saving treatment
    MEDICATION

 for

    end-stage liver disease
    DIAGNOSIS

 in patients with

    Gaucher disease
    DIAGNOSIS

. All four patients have had excellent outcomes from

    liver transplantation
    MEDICATION

 for up to 10 years postprocedure with

    no evidence of Gaucher-related pathology in the graft
    NEG_FINDINGS

.

Enzyme replacement therapy (ERT)
orthotopic liver transplantation
successful liver transplantation
long-term ERT
Liver transplantation
life-saving treatment
liver transplantation


[Atypical recurrent aseptic cutaneous abscesses as the presenting manifestation of Crohn's disease].

We report here a case of chronic inflammatory bowel disease revealed by multiple large cutaneous aseptic distal necrotic ulcers.

A 44-year-old male presented with high fever at 40°C associated with multiple necrotic abcesses located on the distal part of his limbs. They were treated successfully by debridment and dressings associated with antibiotics allowing complete healing after 1 month. Six months later, the patient relapsed on his left hand with a short episode of diarrhoea. A total coloscopy revealed a Crohn's disease. Systemic corticotherapy and azathioprine were administered and complete remission was obtained with a 1-year follow-up.

Skin manifestations that this patient presented were atypical because of their number, size, and location, exclusively distally on the limbs. This report illustrates an unusual presentation of Crohn's disease with multiple necrotic ulcers only located on the patient extremities.

We report here a case of

    chronic inflammatory bowel disease
    DIAGNOSIS

 revealed by

    multiple large cutaneous aseptic distal necrotic ulcers
    SYMPTOMS

.

A

    44-year-old
    AGE

    male
    GENDER

 presented with

    high fever at 40°C
    SYMPTOMS

 associated with

    multiple necrotic abcesses located on the distal part of his limbs
    SYMPTOMS

. They were treated successfully by

    debridment and dressings associated with antibiotics
    MEDICATION

 allowing

    complete healing
    SYMPTOMS

 after 1 month. Six months later, the patient

    relapsed on his left hand
    SYMPTOMS

 with a

    short episode of diarrhoea
    SYMPTOMS

. A

    total coloscopy
    PARACLINICAL

 revealed a

    Crohn's disease
    DIAGNOSIS

.

    Systemic corticotherapy and azathioprine
    MEDICATION

 were administered and

    complete remission
    SYMPTOMS

 was obtained with a 1-year follow-up.

    Skin manifestations
    SYMPTOMS

 that this patient presented were

    atypical because of their number, size, and location, exclusively distally on the limbs
    SYMPTOMS

. This report illustrates an unusual presentation of

    Crohn's disease
    DIAGNOSIS

 with

    multiple necrotic ulcers only located on the patient extremities
    SYMPTOMS

.

chronic inflammatory bowel disease
Crohn's disease
Crohn's disease


Intravenous bisphosphonate treatment and pregnancy: its effects on mother and infant bone health.

Type 1 Gaucher's disease (GD1) is a lysosomal storage disorder associated with disabling bone involvement. The choice treatment for Gaucher's disease is enzyme replacement therapy (ERT). The use of bisphosphonate treatment for osteopenia and osteoporosis has been suggested.

A 22-year-old woman diagnosed with GD1 had received ERT intermittently, depending on availability of the enzyme since the enzyme was not always available. Due to severe bone involvement and multiple vertebral fractures, intravenous administration of 60 mg of pamidronate every 3 months and safe contraception were indicated. Fifteen days after receiving the fourth infusion, the patient informed us she was pregnant. A baby girl was born by cesarean delivery at week 37, showing no evidence of skeletal abnormality or clinical signs of hypocalcemia. The baby developed normally, presenting no significant pathology. At present (age 15 months), height, body weight, and bone mineral density by DXA are within normal range. The mother showed stable total skeleton and right femoral neck bone mineral density (BMD) values, no new fractures, and only ~3% decrease in lumbar spine BMD 15 months post-delivery and after a 1 year breastfeeding period (expected average ~7-8%).

It could be posited that pamidronate exerted a positive protective effect on the mother's skeleton with no evidence of adverse effects on pregnancy or on the baby's health to date.

    Type 1 Gaucher's disease (GD1)
    DIAGNOSIS

 is a

    lysosomal storage disorder
    DIAGNOSIS

 associated with

    disabling bone involvement
    SYMPTOMS

. The choice treatment for

    Gaucher's disease
    DIAGNOSIS

 is

    enzyme replacement therapy (ERT)
    MEDICATION

. The use of

    bisphosphonate treatment
    MEDICATION

 for

    osteopenia
    DIAGNOSIS

 and

    osteoporosis
    SYMPTOMS

 has been suggested.

A

    22-year-old
    AGE

    woman
    GENDER

 diagnosed with

    GD1
    DIAGNOSIS

 had received

    ERT intermittently
    MEDICATION

, depending on availability of the enzyme since the enzyme was not always available. Due to

    severe bone involvement
    SYMPTOMS

 and

    multiple vertebral fractures
    SYMPTOMS

,

    intravenous administration of 60 mg of pamidronate every 3 months
    MEDICATION

 and

    safe contraception
    MEDICATION

 were indicated. Fifteen days after receiving the fourth infusion, the patient informed us

    she
    GENDER

 was

    pregnant
    MEDICATION

. A

    baby girl
    MEDICATION

 was born by

    cesarean delivery at week 37
    MEDICATION

, showing

    no evidence of skeletal abnormality
    NEG_FINDINGS

    or clinical signs of hypocalcemia
    NEG_FINDINGS

. The baby developed normally, presenting

    no significant pathology
    NEG_FINDINGS

. At present (

    age 15 months
    AGE

),

    height, body weight, and bone mineral density by DXA are within normal range
    NEG_FINDINGS

. The

    mother
    GENDER

 showed

    stable total skeleton and right femoral neck bone mineral density (BMD) values
    SYMPTOMS

,

    no new fractures
    NEG_FINDINGS

, and

    only ~3% decrease in lumbar spine BMD 15 months post-delivery
    SYMPTOMS

 and after a 1

    year breastfeeding period
    MEDICATION

 (expected

    average ~7-8%)
    BIOCHEMICAL

.

It could be posited that

    pamidronate
    MEDICATION

 exerted a

    positive protective effect on the mother's skeleton
    SYMPTOMS

 with

    no evidence of adverse effects on pregnancy or on the baby's health
    NEG_FINDINGS

 to date.

Type 1 Gaucher's disease (GD1)
lysosomal storage disorder
Gaucher's disease
osteopenia
GD1


[Anesthetic management in a pregnant woman with type 1 Gaucher disease].

Gaucher disease is a genetic disorder in which the enzyme activity of lysosomal acid beta-glucocerebrosidase is impaired, causing excessive lysosomal storage of glucocerebrosidase in monocytes and macrophages. Coagulation and multiorgan disorders can develop during pregnancy in women with this disorder, affecting anesthetic management. We report the case of a woman with type 1 Gaucher disease who was scheduled for cesarean section. The blood workup showed evidence of hepatosplenomegaly and thrombocytopenia, osteopenia, and gastroesophageal reflux. Epidural anesthesia-analgesia was provided. Surgical conditions and analgesia were both satisfactory and no complications developed after withdrawal of the epidural catheter. We conclude that the management of anesthesia for pregnant women with Gaucher disease will depend on the degree of systemic involvement. Regional anesthesia has been used in many such patients, but there is insufficient literature on which to base guidelines or protocols.

    Gaucher disease
    DIAGNOSIS

 is a

    genetic disorder
    GENETICS

 in which the

    enzyme activity of lysosomal acid beta-glucocerebrosidase is impaired
    BIOCHEMICAL

, causing

    excessive lysosomal storage of glucocerebrosidase in monocytes and macrophages
    MICROSCOPIC

.

    Coagulation
    SYMPTOMS

 and

    multiorgan disorders
    SYMPTOMS

 can develop during

    pregnancy
    AGE

 in

    women
    GENDER

 with this disorder, affecting

    anesthetic management
    MEDICATION

. We report the case of a

    woman
    GENDER

 with

    type 1 Gaucher disease
    DIAGNOSIS

 who was scheduled for

    cesarean section
    MEDICATION

. The

    blood workup
    PARACLINICAL

 showed evidence of

    hepatosplenomegaly
    SYMPTOMS

 and

    thrombocytopenia
    BIOCHEMICAL

,

    osteopenia
    SYMPTOMS

, and

    gastroesophageal reflux
    SYMPTOMS

.

    Epidural anesthesia-analgesia
    MEDICATION

 was provided. Surgical conditions and

    analgesia were both satisfactory
    SYMPTOMS

 and

    no complications developed after withdrawal of the epidural catheter
    NEG_FINDINGS

. We conclude that the management of

    anesthesia
    MEDICATION

 for

    pregnant
    AGE

    women
    GENDER

 with

    Gaucher disease
    DIAGNOSIS

 will depend on the degree of systemic involvement.

    Regional anesthesia
    MEDICATION

 has been used in many such patients, but there is insufficient literature on which to base guidelines or protocols.

Gaucher disease
type 1 Gaucher disease
Gaucher disease

Coagulation
multiorgan disorders
hepatosplenomegaly
osteopenia
gastroesophageal reflux
analgesia were both satisfactory

anesthetic management
cesarean section
Epidural anesthesia-analgesia
anesthesia
Regional anesthesia


An unusual presentation of Gaucher's disease: aortic valve fibrosis in a patient homozygous for a rare G377S mutation.

Gaucher's disease (GD) has variable presentations, but cardiac involvement is a generally uncommon clinical manifestation of the disease. In the past 25 years, the underlying genetic disorder in GD has been well characterized, with almost 300 mutations identified in the glucocerebrosidase gene (GBA). Nevertheless, clear genotype-phenotype correlations have been confirmed only for the most frequent mutations. We present a female patient, who was known to have aortic valve pathology from the age of 30. Despite medical follow up, at the age of 60 she presented with heart failure (NYHA III). At that time echocardiography showed severe fibrosed aortic valve stenosis. Valvuloplasty was planned, when thrombocytopenia, previously considered to be autoimmune, became severe. Anemia and leukopenia were also noted. Moderate splenomegaly and severe bone marrow infiltration were found on MRI. Bone marrow aspiration revealed typical Gaucher cells and the enzyme activity assay confirmed the diagnosis. DNA investigation showed that the patient is homozygous for the G377S mutation. To our knowledge, of all mutations identified so far, only homozygosity for the D409H mutation has been associated with cardiovascular valvular disease in patients with a rare type 3c GD. G377S, found in our patient, is a rare mutation, previously reported as a 'mild' mutation, because of the finding that homoallelic patients were essentialy asymptomatic or had mild disease. Our patient, also homozygous for G377S mutation, had a severe form of type 1 GD, with rare cardiac valve involvement, which is a previously unreported clinical presentation for this mutation. This case further proves that patients with the same genotypes can have different phenotypes, emphasizing the influence of other genetic and/or environmental factors.

    Gaucher's disease (GD)
    DIAGNOSIS

 has variable presentations, but

    cardiac involvement
    SYMPTOMS

 is a generally uncommon clinical manifestation of the disease. In the past 25 years, the underlying

    genetic disorder
    GENETICS

 in

    GD
    DIAGNOSIS

 has been well characterized, with almost 300 mutations identified

    in the glucocerebrosidase gene (GBA)
    GENETICS

. Nevertheless, clear genotype-phenotype correlations have been confirmed only for the most frequent mutations. We present a

    female
    GENDER

 patient, who was known to have

    aortic valve pathology
    SYMPTOMS

 from the

    age of 30
    AGE

.

    Despite medical follow up
    NEG_FINDINGS

, at the

    age of 60
    AGE

    she
    GENDER

 presented with

    heart failure (NYHA III)
    SYMPTOMS

. At that time

    echocardiography
    PARACLINICAL

 showed

    severe fibrosed aortic valve stenosis
    SYMPTOMS

.

    Valvuloplasty
    MEDICATION

 was planned, when

    thrombocytopenia
    BIOCHEMICAL

    , previously considered to be autoimmune
    NEG_FINDINGS

, became

    severe
    BIOCHEMICAL

.

    Anemia
    BIOCHEMICAL

 and

    leukopenia
    BIOCHEMICAL

 were also noted.

    Moderate splenomegaly
    SYMPTOMS

 and

    severe bone marrow infiltration
    MICROSCOPIC

 were found on

    MRI
    PARACLINICAL

.

    Bone marrow aspiration
    PARACLINICAL

 revealed

    typical Gaucher cells
    MICROSCOPIC

 and the

    enzyme activity assay
    PARACLINICAL

 confirmed the diagnosis.

    DNA investigation
    PARACLINICAL

 showed that the patient is

    homozygous for the G377S mutation
    GENETICS

. To our knowledge, of all mutations identified so far, only

    homozygosity for the D409H mutation
    GENETICS

 has been associated with

    cardiovascular valvular disease
    SYMPTOMS

 in patients with a

    rare type 3c GD
    DIAGNOSIS

.

    G377S,
    GENETICS

 found in our patient, is a

    rare mutation
    GENETICS

, previously reported as a 'mild' mutation, because of the finding that

    homoallelic
    GENETICS

 patients were

    essentialy asymptomatic
    NEG_FINDINGS

 or had

    mild disease
    SYMPTOMS

. Our patient, also

    homozygous for G377S mutation
    GENETICS

, had a

    severe form of type 1 GD
    DIAGNOSIS

, with

    rare cardiac valve involvement
    SYMPTOMS

, which is a previously unreported clinical presentation for this mutation. This case further proves that patients with the same genotypes can have different phenotypes, emphasizing the influence of other genetic and/or environmental factors.

Gaucher's disease (GD)
GD
rare type 3c GD
severe form of type 1 GD

cardiac involvement
aortic valve pathology
heart failure (NYHA III)
severe fibrosed aortic valve stenosis
Moderate splenomegaly
cardiovascular valvular disease
mild disease
rare cardiac valve involvement

genetic disorder
in the glucocerebrosidase gene (GBA)
homozygous for the G377S mutation
homozygosity for the D409H mutation
G377S,
rare mutation
homoallelic
homozygous for G377S mutation

thrombocytopenia severe Anemia leukopenia


Bilateral pseudohypopyon as a presenting feature of recurrent diffuse large B-cell lymphoma.

A 55-year-old man with Gaucher disease and B-cell lymphoma developed a white meniscus along the inferior portion of the anterior chamber of both eyes. In one eye, the meniscus was also temporal, reflecting the fact that he had just been lying on his left side. Aspiration of aqueous fluid confirmed that the meniscus was made up of lymphoma cells, indicating that it was a pseudohypopyon. (A true hypopyon is made up of reactive white blood cells.) Despite intensive chemotherapy, the patient expired within 14 weeks of the discovery of the pseudohypopyon. This is the first report of binocular pseudohypopyon confirmed as lymphomatous by flow cytometric immunophenotyping analysis in a patient with diffuse large B-cell lymphoma.

A

    55-year-old
    AGE

    man
    GENDER

 with

    Gaucher disease
    DIAGNOSIS

 and

    B-cell lymphoma
    DIAGNOSIS

 developed a

    white meniscus along the inferior portion of the anterior chamber of both eyes
    SYMPTOMS

. In one eye,

    the meniscus was also temporal
    SYMPTOMS

, reflecting the fact that he had just been lying on his left side.

    Aspiration of aqueous fluid
    PARACLINICAL

 confirmed that

    the meniscus was made up of lymphoma cells
    MICROSCOPIC

, indicating that it was a

    pseudohypopyon
    SYMPTOMS

. (A

    true hypopyon is made up of reactive white blood cells
    SYMPTOMS

.)

    Despite intensive chemotherapy
    NEG_FINDINGS

, the patient

    expired
    SYMPTOMS

 within 14 weeks of the discovery of the

    pseudohypopyon
    SYMPTOMS

. This is the first report of

    binocular pseudohypopyon
    SYMPTOMS

 confirmed as

    lymphomatous
    DIAGNOSIS

 by

    flow cytometric immunophenotyping analysis
    PARACLINICAL

 in a patient with

    diffuse large B-cell lymphoma
    DIAGNOSIS

.

Gaucher disease
B-cell lymphoma
lymphomatous
diffuse large B-cell lymphoma


Exceptional oral manifestations of amyloid light chain protein (AL) systemic amyloidosis.

Oral amyloidosis is usually presented in the tongue and is often associated with multiple myeloma. We present three patients with unusual oral manifestations of primary amyloidosis, which to the best of our knowledge have not been previously published. In two cases the oral manifestation was overt at the time of diagnosis and all cases ended in patient mortality. Since these oral manifestations can contribute to the diagnosis of systemic amyloidosis, clinicians should be made aware of them. Future research should assess the significance of oral manifestation as a prognostic indicator.

    Oral amyloidosis
    DIAGNOSIS

 is usually presented in the tongue and is often associated with

    multiple myeloma
    DIAGNOSIS

. We present three patients with

    unusual oral manifestations
    SYMPTOMS

 of

    primary amyloidosis
    DIAGNOSIS

, which to the best of our knowledge have not been previously published. In two cases the

    oral manifestation
    SYMPTOMS

 was overt at the time of diagnosis and all cases ended in patient mortality. Since these

    oral manifestations
    SYMPTOMS

 can contribute to the diagnosis of

    systemic amyloidosis
    DIAGNOSIS

, clinicians should be made aware of them. Future research should assess the significance of

    oral manifestation
    SYMPTOMS

 as a prognostic indicator.

Oral amyloidosis
multiple myeloma
primary amyloidosis
systemic amyloidosis

unusual oral manifestations
oral manifestation
oral manifestations
oral manifestation


Effects of imiglucerase treatment on traumatic fracture and bone and blood abnormalities in a patient with previously untreated type 1 gaucher disease.

This letter reports on the effect of enzyme replacement therapy with imiglucerase on bone healing and bone and blood abnormalities in a woman with previously untreated type 1 Gaucher disease (GD).

The 49-year-old patient had been diagnosed with GD at the age of 28 years and had previously undergone splenectomy. She presented with pseudarthrosis 14 months after sustaining a traumatic fracture of the tibia and fibula. Therapy was begun with imiglucerase 60 U/kg q2wk. The effects of treatment on bone healing were monitored radiographically, and effects on blood and bone marrow biology were monitored by hemograms, myelograms, and hematopoietic and mesenchymal clonogenic assays.

Objective bone healing was observed starting in the third month of imiglucerase treatment. Blood abnormalities normalized and bone marrow parameters improved over the first 9 months, including a decrease in Gaucher cells, an increase in bone marrow CD34+ cell cloning efficiency, and the appearance of mesenchymal progenitors.

This research letter reports the results of hematologic and bone evaluations during enzyme replacement therapy with imiglucerase in a woman with previously untreated type 1 GD who presented with a traumatic fracture.

This letter reports on the effect of

    enzyme replacement therapy with imiglucerase
    MEDICATION

 on

    bone healing
    SYMPTOMS

 and

    bone and blood abnormalities
    SYMPTOMS

 in a

    woman
    GENDER

 with previously untreated

    type 1 Gaucher disease (GD)
    DIAGNOSIS

.

The

    49-year-old
    AGE

 patient had been diagnosed with

    GD
    DIAGNOSIS

 at the

    age of 28 years
    AGE

 and had

    previously undergone splenectomy
    MEDICATION

.

    She
    GENDER

 presented with

    pseudarthrosis
    DIAGNOSIS

 14 months after

    sustaining a traumatic fracture of the tibia and fibula
    MEDICATION

. Therapy was begun with

    imiglucerase 60 U/kg q2wk
    MEDICATION

. The effects of treatment on

    bone healing
    SYMPTOMS

 were monitored

    radiographically
    PARACLINICAL

, and effects on blood and bone marrow biology were monitored by

    hemograms, myelograms
    PARACLINICAL

, and

    hematopoietic and mesenchymal clonogenic assays
    PARACLINICAL

.

    Objective bone healing
    SYMPTOMS

 was observed starting in the third month of

    imiglucerase treatment
    MEDICATION

.

    Blood abnormalities normalized
    BIOCHEMICAL

 and

    bone marrow parameters improved
    MICROSCOPIC

 over the first 9

    months
    BIOCHEMICAL

, including a

    decrease in Gaucher cells
    MICROSCOPIC

, an

    increase in bone marrow CD34+ cell cloning efficiency, and the appearance of mesenchymal progenitors
    MICROSCOPIC

.

This research letter reports the results of

    hematologic and bone evaluations
    PARACLINICAL

 during

    enzyme replacement therapy with imiglucerase
    MEDICATION

 in a

    woman
    GENDER

 with

    previously untreated type 1 GD
    NEG_FINDINGS

 who presented with a

    traumatic fracture
    SYMPTOMS

.

bone healing
bone and blood abnormalities
bone healing
Objective bone healing
traumatic fracture

type 1 Gaucher disease (GD)
GD
pseudarthrosis


Spectral OCT analysis in Bietti crystalline dystrophy.

To report the analysis of the cornea and the macular retina using both time domain (TD-OCT) and Fourier domain optical coherence tomography (FD-OCT) in a case of Bietti crystalline dystrophy (BCD).

This is a case study of a 32-year-old woman who presented with moderate visual loss in both eyes with nyctalopia. She had a complete ophthalmologic examination including fundus examination. She also underwent fluoroangiography, Goldmann perimetry, electroretinography/electrooculography, and both TD-OCT and FD-OCT examinations.

Large atrophy of retinal pigment epithelium and choroidal sclerosis were observed on both funduscopy and angiography. Microcrystals deposits were observed in the cornea and in the retina. Visual fields were constricted and electrophysiology was greatly impaired. BCD was diagnosed. TD-OCT examination was normal whereas FD-OCT revealed modifications of the outer retina and the presence of numerous lesions corresponding to microcrystals deposits in all retinal layers. The diameter of the deposits was comprised between 18 and 100 microm.

FD-OCT was superior to TD-OCT in detecting and localizing microcrystals in BCD. FD-OCT might be useful in the understanding and the follow-up of this rare disease.

To report the

    analysis of the cornea and the macular retina using both time domain (TD-OCT) and Fourier domain optical coherence tomography (FD-OCT)
    PARACLINICAL

 in a case of

    Bietti crystalline dystrophy (BCD)
    DIAGNOSIS

.

This is a case study of a

    32-year-old
    AGE

    woman
    GENDER

 who presented with

    moderate visual loss in both eyes
    SYMPTOMS

 with

    nyctalopia
    SYMPTOMS

.

    She
    GENDER

 had a

    complete ophthalmologic examination
    PARACLINICAL

 including

    fundus examination
    PARACLINICAL

.

    She
    GENDER

 also underwent

    fluoroangiography
    PARACLINICAL

,

    Goldmann perimetry
    PARACLINICAL

,

    electroretinography/electrooculography
    PARACLINICAL

, and

    both TD-OCT and FD-OCT examinations
    PARACLINICAL

.

    Large atrophy of retinal pigment epithelium
    SYMPTOMS

 and

    choroidal sclerosis
    SYMPTOMS

 were observed on both

    funduscopy
    PARACLINICAL

 and

    angiography
    PARACLINICAL

.

    Microcrystals deposits were observed in the cornea and in the retina
    MICROSCOPIC

.

    Visual fields were constricted
    SYMPTOMS

 and

    electrophysiology was greatly impaired
    SYMPTOMS

.

    BCD
    DIAGNOSIS

 was diagnosed.

    TD-OCT examination was normal
    NEG_FINDINGS

 whereas

    FD-OCT
    PARACLINICAL

 revealed

    modifications of the outer retina
    SYMPTOMS

 and the

    presence of numerous lesions corresponding to microcrystals deposits in all retinal layers
    SYMPTOMS

. The

    diameter of the deposits was comprised between 18 and 100 microm.
    SYMPTOMS

    FD-OCT
    PARACLINICAL

 was superior to

    TD-OCT
    PARACLINICAL

 in detecting and localizing

    microcrystals
    SYMPTOMS

 in

    BCD
    DIAGNOSIS

.

    FD-OCT
    PARACLINICAL

 might be useful in the understanding and the follow-up of this rare disease.

Bietti crystalline dystrophy (BCD)
BCD
BCD


Gaucher's disease type I: a disease masked by the presence of abnormal laboratory tests common to primary liver disease.

Gaucher's disease (GD) may go undiagnosed for many years, leading to severe complications that are preventable or reversible by enzyme replacement therapy with imiglucerase. GD is associated with cytopenia, bone complications, hepatosplenomegaly, hypermetabolism, and hyperactivity of the immune system manifested by polyclonal hyper gamma-globulinemia and an increased incidence of monoclonal gammopathies. High ferritin and presence of autoimmune antibodies may present and because of these abnormalities, clinical similarities with primary liver diseases may occur. We report on two patients who suffered diagnostic delay that could potentially lead to life-threatening manifestations of GD. Potential complications include: avascular necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure, and liver pathology. Physician awareness will increase the likelihood of prompt detection of GD and improve its management.

    Gaucher's disease (GD)
    DIAGNOSIS

 may go undiagnosed for many years, leading to severe complications that are preventable or reversible by

    enzyme replacement therapy with imiglucerase
    MEDICATION

.

    GD
    DIAGNOSIS

 is associated with

    cytopenia
    BIOCHEMICAL

,

    bone complications
    SYMPTOMS

,

    hepatosplenomegaly
    SYMPTOMS

,

    hypermetabolism
    SYMPTOMS

, and

    hyperactivity of the immune system
    BIOCHEMICAL

 manifested by

    polyclonal hyper gamma-globulinemia
    BIOCHEMICAL

 and an increased incidence of

    monoclonal gammopathies
    BIOCHEMICAL

.

    High ferritin
    BIOCHEMICAL

 and

    presence of autoimmune antibodies
    BIOCHEMICAL

 may present and because of these abnormalities,

    clinical similarities with primary liver diseases
    SYMPTOMS

 may occur. We report on two patients who suffered diagnostic delay that could potentially lead to

    life-threatening manifestations
    SYMPTOMS

 of

    GD
    DIAGNOSIS

. Potential complications include:

    avascular necrosis
    SYMPTOMS

,

    severe bleeding
    SYMPTOMS

,

    chronic bone pain
    SYMPTOMS

,

    life-threatening sepsis
    SYMPTOMS

,

    pathologic fractures
    SYMPTOMS

,

    growth failure
    SYMPTOMS

, and

    liver pathology
    SYMPTOMS

. Physician awareness will increase the likelihood of prompt detection of

    GD
    DIAGNOSIS

 and improve its management.

cytopenia
hyperactivity of the immune system
polyclonal hyper gamma-globulinemia
monoclonal gammopathies
High ferritin
presence of autoimmune antibodies


Type-3 Gaucher disease with bilateral necrosis of the neck of femur: a case report.

Though Gauchers disease (G.D.), a lipid storage disease is most commonly encountered by the hematologist but we present a case of G.D. type-3 which is rare in Indian subcontinent.

A 36-year-old Hindu, Indian male patient presented with bony pain, kyphosis, dragging sensation in the abdomen, dementia and ptosis of the left eyelid for one year. Clinical examination and history pointed to be a lipid storage disease. Radiological examination showed bilateral necrosis of the neck of femur. A final diagnosis of G.D. type-3 with bilateral necrosis of the femur neck was reported after examining the bone marrow smears. Unfortunately, we were unable to do the enzyme study as the patient was lost in the follow-up.

G.D. type-3 with bilateral necrosis of femur neck is rare in our sub-continent. We are adding a new case to stress the importance of early recognition by clinical manifestation and finding of G.C. which is hallmark in the diagnosis of G.D.

Though

    Gauchers disease (G.D.)
    DIAGNOSIS

, a

    lipid storage disease
    DIAGNOSIS

 is most commonly encountered by the

    hematologist
    PARACLINICAL

 but we present a case of

    G.D. type-3
    DIAGNOSIS

 which is rare in

    Indian subcontinent
    ETHNICITY

.

A

    36-year-old
    AGE

    Hindu
    ETHNICITY

,

    Indian
    ETHNICITY

    male
    GENDER

 patient presented with

    bony pain
    SYMPTOMS

,

    kyphosis
    SYMPTOMS

,

    dragging sensation in the abdomen
    SYMPTOMS

,

    dementia
    SYMPTOMS

 and

    ptosis of the left eyelid
    SYMPTOMS

 for one year.

    Clinical examination
    PARACLINICAL

 and history pointed to be a

    lipid storage disease
    DIAGNOSIS

.

    Radiological examination
    PARACLINICAL

 showed

    bilateral necrosis of the neck of femur
    SYMPTOMS

. A final diagnosis of

    G.D. type-3
    DIAGNOSIS

 with

    bilateral necrosis of the femur neck
    SYMPTOMS

 was reported after

    examining the bone marrow smears
    PARACLINICAL

.

    Unfortunately, we were unable to do the enzyme study
    NEG_FINDINGS

 as the patient was

    lost in the follow-up
    NEG_FINDINGS

.

    G.D. type-3
    DIAGNOSIS

 with

    bilateral necrosis of femur neck
    SYMPTOMS

 is rare in our

    sub-continent
    ETHNICITY

. We are adding a new case to stress the importance of early recognition by clinical manifestation and finding of

    G.C.
    BIOCHEMICAL

 which is hallmark in the diagnosis of

    G.D.
    DIAGNOSIS

Gauchers disease (G.D.)
lipid storage disease
G.D. type-3
lipid storage disease
G.D. type-3
G.D. type-3
G.D.

Indian subcontinent
Hindu
Indian
sub-continent

bony pain
kyphosis
dragging sensation in the abdomen
dementia
ptosis of the left eyelid
bilateral necrosis of the neck of femur
bilateral necrosis of the femur neck
bilateral necrosis of femur neck


Pseudogaucher cells obscuring multiple myeloma: a case report.

Gaucher-like or pseudo-Gaucher cells have been noted in a variety of conditions including acute lymphoblastic leukemia, Hodgkin's disease, thalassemia, and multiple myeloma. They have an eccentric, lobulated nucleus, foamy cytoplasm but lack the tubular inclusions seen in Gaucher cells. The pseudo-Gaucher cells have distinct appearances on electron microscopy which distinguish them from true Gaucher cells.Increased pseudo-Gaucher cells probably reflects the increased load of leukocyte membrane derived glucosylceramide presented to macrophages under conditions of high cell turnover when the normal pathways for its removal may be saturated.We present a case of a 72-year-old Indian Aryan female, in which the bone marrow contained sheets of histiocytes with features mimicking gaucher cells. These pseudo-Gaucher cells obscured neoplastic plasma cells causing diagnostic difficulty.

    Gaucher-like or pseudo-Gaucher cells
    MICROSCOPIC

 have been noted in a variety of conditions including

    acute lymphoblastic leukemia
    DIAGNOSIS

,

    Hodgkin's disease
    DIAGNOSIS

,

    thalassemia
    DIAGNOSIS

, and

    multiple myeloma
    DIAGNOSIS

. They have an

    eccentric, lobulated nucleus
    MICROSCOPIC

,

    foamy cytoplasm
    MICROSCOPIC

 but

    lack the tubular inclusions seen in Gaucher cells
    MICROSCOPIC

. The

    pseudo-Gaucher cells
    MICROSCOPIC

 have distinct appearances on

    electron microscopy
    PARACLINICAL

 which distinguish them from

    true Gaucher cells
    MICROSCOPIC

.

    Increased pseudo-Gaucher cells
    MICROSCOPIC

 probably reflects the

    increased load of leukocyte membrane derived glucosylceramide presented to macrophages
    MICROSCOPIC

 under conditions of high cell turnover when the

    normal pathways for its removal may be saturated
    NEG_FINDINGS

.We present a case of a

    72-year-old
    AGE

    Indian
    ETHNICITY

    Aryan
    ETHNICITY

    female
    GENDER

, in which

    the bone marrow contained sheets of histiocytes with features mimicking gaucher cells
    MICROSCOPIC

. These

    pseudo-Gaucher cells obscured neoplastic plasma cells
    MICROSCOPIC

 causing diagnostic difficulty.

acute lymphoblastic leukemia
Hodgkin's disease
thalassemia
multiple myeloma


Pediatric Gaucher disease type I and mild growth hormone deficiency: a new feature?

A 5-year-old girl was referred to the Department of Pediatrics and Neonatology, Guglielmo da Saliceto Hospital, Italy, because of growth retardation. Clinical and laboratory investigations showed pallor, hepatosplenomegaly, anemia and low/normal platelet count. Further investigations led to the diagnosis of Gaucher disease (GD). We believe this is the first report of growth hormone deficiency in a growth-retarded child with GD. After 1 year of imiglucerase replacement enzyme therapy, her bone age had normalized, linear growth rate had accelerated, and insulin growth factor-1 (IGF-1) and, perhaps more interestingly, growth hormone deficiency, had normalized. While the pathophysiological mechanisms underlying compromised growth in GD are poorly understood, the response to imiglucerase reported in this patient suggests that growth hormone deficiency is related to the underlying metabolic disorder in GD, rather than a primary endocrine pathology. Growth hormone deficiency adds to an already extensive list of possible clinical manifestations of this heterogeneous and complex disorder.

A

    5-year-old
    AGE

    girl
    GENDER

 was referred to the Department of Pediatrics and

    Neonatology
    PARACLINICAL

, Guglielmo da Saliceto Hospital,

    Italy
    ETHNICITY

, because of

    growth retardation
    SYMPTOMS

.

    Clinical and laboratory investigations
    PARACLINICAL

 showed

    pallor
    SYMPTOMS

,

    hepatosplenomegaly
    SYMPTOMS

,

    anemia
    BIOCHEMICAL

 and

    low/normal platelet count
    BIOCHEMICAL

. Further investigations led to the diagnosis of

    Gaucher disease (GD)
    DIAGNOSIS

. We believe this is the first report of

    growth hormone deficiency
    BIOCHEMICAL

 in a

    growth-retarded
    AGE

    child
    AGE

 with

    GD
    DIAGNOSIS

. After

    1 year of imiglucerase replacement enzyme therapy
    MEDICATION

,

    her
    GENDER

    bone age had normalized
    SYMPTOMS

,

    linear growth rate had accelerated
    SYMPTOMS

, and

    insulin growth factor-1 (IGF-1) and
    BIOCHEMICAL

, perhaps more interestingly,

    growth hormone deficiency, had normalized
    BIOCHEMICAL

. While the pathophysiological mechanisms underlying

    compromised growth
    SYMPTOMS

 in

    GD
    DIAGNOSIS

 are poorly understood, the response to

    imiglucerase
    MEDICATION

 reported in this patient suggests that

    growth hormone deficiency
    BIOCHEMICAL

 is related to the underlying

    metabolic disorder
    DIAGNOSIS

 in

    GD
    DIAGNOSIS

, rather than a primary

    endocrine pathology
    DIAGNOSIS

.

    Growth hormone deficiency
    BIOCHEMICAL

 adds to an already extensive list of possible clinical manifestations of this heterogeneous and complex disorder.

growth retardation
pallor
hepatosplenomegaly
bone age had normalized
linear growth rate had accelerated
compromised growth

Gaucher disease (GD)
GD
GD
metabolic disorder
GD
endocrine pathology


Abnormal nonstoring capillary endothelium: a novel feature of Gaucher disease. Ultrastructural study of dermal capillaries.

Ultrastructural study of skin biopsies in two cases of Gaucher disease (GD) patients (types II and III) revealed hitherto unknown alteration of the blood capillary endothelial cells (ECs) featured by hypertrophy and numerous subplasmalemmal microvesicles underneath both the apical and basal membranes. There was also prominent apical membrane folding with formation of filiform and large cytoplasmic projections, with occasional transcapillary cytoplasmic bridges. Similar, though less frequently expressed, changes were manifested at the basal membrane by numerous cytoplasmic projections into the subendothelial space. Regressive changes with EC breakdown were rare. Lysosomal storage was always absent. Besides EC hypertrophy, there was also increased EC density in the capillary lumen, leading to pronounced changes in capillary architecture with loose or incomplete EC anchoring. There were also signs of EC sprouting. Some pericytes displayed an increase in size and number of cytoplasmic processes, which often extended into distant pericapillary regions. The spectrum of changes suggests that a significant positive growth effect on EC occurs in GD. The putative mechanisms triggered by GBA1 deficiency leading to EC involvement are discussed. The authors are well aware of the fact the results, based on a nontraditional type of bioptic samples, are preliminary, but they are worth following, as further ultrastructural and functional studies of blood endothelium in GD may open a novel field in molecular cell pathophysiology of the disorder: endothelial dysfunction.

    Ultrastructural study of skin biopsies
    PARACLINICAL

 in two cases of

    Gaucher disease (GD)
    DIAGNOSIS

 patients (

    types II and III)
    DIAGNOSIS

 revealed hitherto unknown

    alteration of the blood capillary endothelial cells (ECs)
    MICROSCOPIC

 featured by

    hypertrophy and numerous subplasmalemmal microvesicles underneath both the apical and basal membranes
    MICROSCOPIC

. There was also

    prominent apical membrane folding with formation of filiform and large cytoplasmic projections, with occasional transcapillary cytoplasmic bridges
    MICROSCOPIC

. Similar, though less frequently expressed, changes were manifested

    at the basal membrane
    MICROSCOPIC

 by

    numerous cytoplasmic projections into the subendothelial space
    MICROSCOPIC

.

    Regressive changes with EC breakdown
    SYMPTOMS

 were rare.

    Lysosomal storage was always absent
    NEG_FINDINGS

. Besides

    EC hypertrophy
    MICROSCOPIC

, there was also

    increased EC density in the capillary lumen
    MICROSCOPIC

, leading to

    pronounced changes in capillary architecture with loose or incomplete EC anchoring
    SYMPTOMS

. There were also signs of

    EC sprouting
    MICROSCOPIC

.

    Some pericytes displayed an increase in size and number of cytoplasmic processes, which often extended into distant pericapillary regions
    MICROSCOPIC

. The spectrum of changes suggests that a

    significant positive growth effect on EC
    SYMPTOMS

 occurs in

    GD
    DIAGNOSIS

. The putative mechanisms triggered by

    GBA1 deficiency
    BIOCHEMICAL

 leading to

    EC involvement
    SYMPTOMS

 are discussed. The authors are well aware of the fact the results, based on a nontraditional type of bioptic samples, are preliminary, but they are worth following, as further

    ultrastructural and functional studies of blood endothelium
    PARACLINICAL

 in

    GD
    DIAGNOSIS

 may open a novel field in molecular cell pathophysiology of the disorder:

    endothelial dysfunction
    SYMPTOMS

.

Gaucher disease (GD)
types II and III)
GD
GD


[High dose of enzyme replacement therapy was successful for the pulmonary involvement in a case of type 2 Gaucher disease].

Pulmonary involvement is a serious complication in Gaucher disease, as is neuronopathic involvement. Few reports are available, however, on the frequency, clinical course and therapy for pulmonary involvement in patients with Gaucher disease. We report a case of type 2 Gaucher disease with severe hepatosplenomegaly, anemia, hypertonia, and psychomotor retardation. The diagnosis of Gaucher disease was confirmed by the presence of Gaucher cells in bone marrow and low serum beta-glucocerebrosidase activity (patient, 0.8; control, 4.1-9.7 nmol/mg.protein/hr) at the age of 1 year. The patient's genotype is L444P/unknown. Enzyme replacement therapy (ERT) with intravenous imiglucerase at 78 U/kg/2weeks was started, and hepatosplenomegaly and laboratory abnormalities were markedly improved after 6 months of therapy. After 8 months of therapy, respiratory impairment appeared together with a decrease of tidal volume and low SpO2 during sleep. Serum acid phosphatase and angiotensin converting enzyme levels mildly increased, and radiological findings showed bilateral ground-glass appearance without signs of respiratory infection. With the diagnosis of progressive pulmonary involvement in Gaucher disease, we increased the dosage of imiglucerase from 50 to 75 U/kg/2 weeks. After a month, respiratory symptoms and CT findings of ground-glass appearance remarkably improved, but interlobular septal and intralobular interstitial thickening persisted. The maximum permitted dosage of imiglucerase in Japan is 60 U/kg/2 weeks. Based on our experience with this case, we propose that a higher ERT dosage would be uselul for serious pulmonary involvement.

    Pulmonary involvement
    SYMPTOMS

 is a serious complication in

    Gaucher disease
    DIAGNOSIS

, as is

    neuronopathic involvement
    SYMPTOMS

. Few reports are available, however, on the frequency, clinical course and therapy for

    pulmonary involvement
    SYMPTOMS

 in patients with

    Gaucher disease
    DIAGNOSIS

. We report a case of

    type 2 Gaucher disease
    DIAGNOSIS

 with

    severe hepatosplenomegaly
    SYMPTOMS

,

    anemia
    BIOCHEMICAL

,

    hypertonia
    SYMPTOMS

, and

    psychomotor retardation
    SYMPTOMS

. The diagnosis of

    Gaucher disease
    DIAGNOSIS

 was confirmed by the

    presence of Gaucher cells in bone marrow
    MICROSCOPIC

 and

    low serum beta-glucocerebrosidase activity (patient, 0.8; control, 4.1-9.7 nmol/mg.protein/hr)
    BIOCHEMICAL

 at the

    age of 1 year
    AGE

. The patient's

    genotype is L444P/unknown
    GENETICS

.

    Enzyme replacement therapy (ERT) with intravenous imiglucerase at 78 U/kg/2weeks
    MEDICATION

 was started, and

    hepatosplenomegaly
    SYMPTOMS

 and

    laboratory abnormalities
    BIOCHEMICAL

    were markedly improved
    SYMPTOMS

 after

    6 months of therapy
    MEDICATION

. After

    8 months of therapy
    MEDICATION

,

    respiratory impairment
    SYMPTOMS

 appeared together with a

    decrease of tidal volume
    SYMPTOMS

 and

    low SpO2 during sleep
    SYMPTOMS

.

    Serum acid phosphatase and angiotensin converting enzyme levels mildly increased
    BIOCHEMICAL

, and

    radiological findings
    PARACLINICAL

 showed

    bilateral ground-glass appearance
    SYMPTOMS

    without signs of respiratory infection
    NEG_FINDINGS

. With the diagnosis of

    progressive pulmonary involvement
    SYMPTOMS

 in

    Gaucher disease
    DIAGNOSIS

, we

    increased the dosage of imiglucerase from 50 to 75 U/kg/2 weeks
    MEDICATION

. After a month,

    respiratory symptoms
    SYMPTOMS

 and

    CT findings of ground-glass appearance remarkably improved
    SYMPTOMS

, but

    interlobular septal and intralobular interstitial thickening
    SYMPTOMS

 persisted. The maximum permitted

    dosage of imiglucerase
    MEDICATION

 in

    Japan
    ETHNICITY

    is 60 U/kg/2 weeks
    MEDICATION

. Based on our experience with this case, we propose that a

    higher ERT dosage
    MEDICATION

 would be uselul for

    serious pulmonary involvement
    DIAGNOSIS

.

Gaucher disease
Gaucher disease
type 2 Gaucher disease
Gaucher disease
Gaucher disease
serious pulmonary involvement


Munchausen syndrome by proxy mimicking as Gaucher disease.

Although rare, Munchausen syndrome by proxy (MBP) is a potentially life-threatening form of child abuse. Here, we report a 19-month-old female infant who presented with hepatosplenomegaly, anemia, thrombocytopenia, and recurrent septicemia. She was initially thought to have myelodysplastic syndrome. Further hematological and immunological investigations revealed no cause. beta-Glucosylceramidase enzyme activity on dried blood spot was suggestive of Gaucher disease. However, the enzyme level on cultured skin fibroblast was not consistent with Gaucher disease. The first hint about MBP was the recurrent sepsis with numerous gram negative rods. Furthermore, the mother's behavior and health history raised our suspicion about MBP. The child showed significant improvement after she was separated from the mother for a week. Finally, the mother confessed that she was spitting in local herbs and injecting it into the central line. This is, to our knowledge, the first report of MBP resembling in its presentation Gaucher disease. This case should alert the general and specialized pediatricians about MBP, as it may mimic metabolic diseases like Gaucher disease.

Although rare,

    Munchausen syndrome by proxy (MBP)
    DIAGNOSIS

 is a potentially

    life-threatening form of child abuse
    SYMPTOMS

. Here, we report a

    19-month-old
    AGE

    female
    GENDER

    infant
    AGE

 who presented with

    hepatosplenomegaly
    SYMPTOMS

,

    anemia
    BIOCHEMICAL

,

    thrombocytopenia
    BIOCHEMICAL

, and

    recurrent septicemia
    SYMPTOMS

.

    She
    GENDER

 was

    initially thought to have myelodysplastic syndrome
    NEG_FINDINGS

. Further

    hematological and immunological investigations revealed no cause
    NEG_FINDINGS

.

    beta-Glucosylceramidase enzyme activity on dried blood spot
    BIOCHEMICAL

 was suggestive of

    Gaucher disease
    DIAGNOSIS

. However, the

    enzyme level on cultured skin fibroblast was not consistent with Gaucher disease
    NEG_FINDINGS

. The first hint about

    MBP
    DIAGNOSIS

 was the

    recurrent sepsis with numerous gram negative rods
    SYMPTOMS

. Furthermore, the mother's behavior and health history raised our suspicion about

    MBP
    DIAGNOSIS

. The

    child
    AGE

 showed

    significant improvement
    SYMPTOMS

 after

    she
    GENDER

    was separated from the mother for a week
    MEDICATION

. Finally, the

    mother
    GENDER

 confessed that

    she
    GENDER

 was

    spitting in local herbs and injecting it into the central line
    MEDICATION

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

    MBP
    DIAGNOSIS

 resembling in its presentation

    Gaucher disease
    DIAGNOSIS

. This case should alert the general and

    specialized pediatricians
    PARACLINICAL

 about

    MBP
    DIAGNOSIS

, as it may mimic

    metabolic diseases
    DIAGNOSIS

 like

    Gaucher disease
    DIAGNOSIS

.

Munchausen syndrome by proxy (MBP)
Gaucher disease
MBP
MBP
MBP
Gaucher disease
MBP
metabolic diseases
Gaucher disease


Gaucher disease patient with myoclonus epilepsy and a novel mutation.

The N188S mutation in Gaucher disease is associated with myoclonus epilepsy. We performed genetic analysis on a patient with progressive myoclonus epilepsy, who had received antiepileptic drugs for over 10 years. We detected N188S/G199D on the gene encoding glucocerebrosidase. Mutant proteins carrying each mutation were expressed in COS-1 cells (a commonly used cell line which derives from kidney cells of the African green monkey). Measurements of enzymatic activity and Western blotting analysis were performed. When residual activities were measured, glucocerebrosidase with the N188S mutation exhibited 50% activity of the wild type, and with G199D, 7.4%. Neither mutation influenced the stability of the enzyme protein. These data suggested a diagnosis of Gaucher disease for this patient, and indicated that G199D is a novel mutation.

The

    N188S mutation
    GENETICS

 in

    Gaucher disease
    DIAGNOSIS

 is associated with

    myoclonus epilepsy
    SYMPTOMS

. We performed

    genetic analysis
    PARACLINICAL

 on a patient with

    progressive myoclonus epilepsy
    SYMPTOMS

, who had

    received antiepileptic drugs for over 10 years
    MEDICATION

. We detected

    N188S/G199D on the gene encoding glucocerebrosidase
    GENETICS

. Mutant proteins carrying each mutation were expressed in COS-1 cells (a commonly used cell line which derives from kidney cells of the African green monkey).

    Measurements of enzymatic activity
    PARACLINICAL

 and

    Western blotting analysis
    PARACLINICAL

 were performed. When

    residual activities
    BIOCHEMICAL

 were measured,

    glucocerebrosidase with the N188S mutation
    BIOCHEMICAL

    exhibited 50% activity of the wild type
    BIOCHEMICAL

, and with

    G199D
    GENETICS

,

    7.4%
    BIOCHEMICAL

.

    Neither mutation influenced the stability of the enzyme protein
    NEG_FINDINGS

. These data suggested a diagnosis of

    Gaucher disease
    DIAGNOSIS

 for this patient, and indicated that

    G199D is a novel mutation
    GENETICS

.

myoclonus epilepsy
progressive myoclonus epilepsy


Intrapelvic mass causing femoral compression neuropathy in a patient with Gaucher disease: a case report.

Gaucher disease is a lysosomal storage disorder in which glucocerebroside accumulates within the macrophages in any part of the body. Varying degrees of skeletal involvement may occur besides anemia, coagulation abnormalities and hepatosplenomegaly. Most of the factors influencing the quality of life in a patient with Gaucher disease are related to bone involvement. Gaucher cell deposits may extrude through cortical erosions and cause soft tissue masses around bones which are involved by the disease. We present a 38-year-old female patient with Gaucher disease who had a large intrapelvic mass originating from left iliac bone causing femoral compression neuropathy. The classification of disease is based on neurological involvement and if symptoms exist whether the symptoms are acute or subacute. The neurological impairment caused by compression by a tumor should be distinguished from the ones reported in neurogenic forms of the disease.

    Gaucher disease
    DIAGNOSIS

 is a

    lysosomal storage disorder
    DIAGNOSIS

 in which

    glucocerebroside accumulates within the macrophages in any part of the body
    MICROSCOPIC

. Varying degrees of

    skeletal involvement
    SYMPTOMS

 may occur besides

    anemia
    BIOCHEMICAL

,

    coagulation abnormalities
    BIOCHEMICAL

 and

    hepatosplenomegaly
    SYMPTOMS

. Most of the factors influencing the quality of life in a patient with

    Gaucher disease
    DIAGNOSIS

 are related to

    bone involvement
    SYMPTOMS

.

    Gaucher cell deposits
    MICROSCOPIC

 may

    extrude through cortical erosions
    MICROSCOPIC

 and cause

    soft tissue masses around bones which are involved by the disease
    SYMPTOMS

. We present a

    38-year-old
    AGE

    female
    GENDER

 patient with

    Gaucher disease
    DIAGNOSIS

 who had a

    large intrapelvic mass originating from left iliac bone
    SYMPTOMS

 causing

    femoral compression neuropathy
    SYMPTOMS

. The classification of disease is based on

    neurological involvement
    SYMPTOMS

 and if symptoms exist whether the symptoms are acute or

    subacute
    SYMPTOMS

. The

    neurological impairment caused by compression by a tumor
    SYMPTOMS

 should be distinguished from the ones reported in

    neurogenic forms of the disease
    DIAGNOSIS

.

Gaucher disease
lysosomal storage disorder
Gaucher disease
Gaucher disease
neurogenic forms of the disease


Total hip replacement in Gaucher's disease: effects of enzyme replacement therapy.

Total hip replacement in patients with Gaucher's disease with symptomatic osteonecrosis of the femoral head is controversial because of the high early failure rates. We describe four patients who had an uncemented total hip replacement following enzyme replacement therapy for a median of two years and one month (1 to 9.8 years) prior to surgery, and who remained on treatment. At operation, the bone had a normal appearance and consistency. Histopathological examination showed that, compared with previous biopsies of untreated Gaucher's disease, the Gaucher cell infiltrate had decreased progressively with therapy, being replaced by normal adipose tissue. The surfaces of viable bone beyond the osteonecrotic areas showed osteoblasts, indicating remodelling. In one case acetabular revision was carried out after 11 years and eight months. The three remaining patients had a mean follow-up of six years and four months (3.3 to 12 years). We recommend initiating enzyme replacement therapy at least one to two years prior to total hip replacement to facilitate bone remodelling and to allow implantation of uncemented components in these young patients.

    Total hip replacement
    MEDICATION

 in patients with

    Gaucher's disease
    DIAGNOSIS

 with

    symptomatic osteonecrosis of the femoral head
    SYMPTOMS

 is controversial because of the high early failure rates. We describe four patients who had an

    uncemented total hip replacement following enzyme replacement therapy for a median of two years and one month (1 to 9.8 years) prior to surgery
    MEDICATION

, and who

    remained on treatment
    MEDICATION

. At operation, the

    bone had a normal appearance and consistency
    SYMPTOMS

.

    Histopathological examination
    PARACLINICAL

 showed that, compared with previous biopsies of untreated

    Gaucher's disease
    DIAGNOSIS

,

    the Gaucher cell infiltrate had decreased progressively
    MICROSCOPIC

 with therapy

    , being replaced by normal adipose tissue
    MICROSCOPIC

.

    The surfaces of viable bone beyond the osteonecrotic areas showed osteoblasts, indicating remodelling
    MICROSCOPIC

. In one case

    acetabular revision was carried out after 11 years and eight months
    MEDICATION

. The three remaining patients had a mean

    follow-up of six years and four months (3.3 to 12 years
    PARACLINICAL

). We recommend

    initiating enzyme replacement therapy at least one to two years prior to total hip replacement
    MEDICATION

 to facilitate

    bone remodelling
    MEDICATION

 and to allow

    implantation of uncemented components
    MEDICATION

 in these

    young
    AGE

 patients.


Effective desensitization to imiglucerase in a patient with type I Gaucher disease.

We describe a child who had anaphylactic hypersensitivity to imiglucerase therapy for Gaucher disease. Treatment was stopped and symptoms returned. After immune desensitization to imiglucerase using a rush protocol, the patient was able to resume treatment and has not had further hypersensitivity complications to date.

We describe a

    child
    AGE

 who had

    anaphylactic hypersensitivity to imiglucerase therapy
    SYMPTOMS

 for

    Gaucher disease
    DIAGNOSIS

.

    Treatment was stopped
    MEDICATION

 and

    symptoms returned
    SYMPTOMS

. After

    immune desensitization to imiglucerase using a rush protocol
    MEDICATION

, the patient was able to

    resume treatment
    MEDICATION

 and has

    not had further hypersensitivity complications
    NEG_FINDINGS

 to date.


Substrate deprivation therapy in juvenile Sandhoff disease.

Substrate deprivation therapy has been successfully applied in a number of lysosomal storage diseases, such as Gaucher disease. So far only limited experience is available in Sandhoff disease. We initiated substrate deprivation therapy in one male patient, who initially presented at the age of 3.5 years with epilepsy and regression in motor skills and speech development. Juvenile Sandhoff disease was diagnosed on the basis of a decreased hexosaminidase activity in leukocytes and a homozygous HEXB gene mutation. After the epilepsy was controlled, the clinical course remained stable for years, defined by a mild proximal myopathy and stable mental retardation. At 14 years of age the patient experienced a second episode with progressively worsening general condition with diminishing muscle power and progressive ataxia. Treatment was started with the N-alkylated imino sugar miglustat, inhibiting the glucosylceramide synthase, an essential enzyme for the synthesis of glycosphingolipids. Diarrhoea was treated with lactose restriction. We performed detailed biochemical investigations, motor and mental development analysis, brain imaging, organ function studies and quality of life score prior to and at different time points after start of the treatment. Two years after the initiation of therapy the patient has a stable neurological picture without further regression in his motor development, ataxia or intelligence. There is a subjective improvement in the fine motor skills and walking up the stairs but no change in the quality of life score. Under treatment with miglustat the clinical course in our patient with Sandhoff disease did not further deteriorate.

    Substrate deprivation therapy
    MEDICATION

 has been successfully applied in a number of

    lysosomal storage diseases
    DIAGNOSIS

, such as

    Gaucher disease
    DIAGNOSIS

. So far only limited experience is available in

    Sandhoff disease
    DIAGNOSIS

. We initiated

    substrate deprivation therapy
    MEDICATION

 in one

    male
    GENDER

 patient, who initially presented at the

    age of 3.5 years
    AGE

 with

    epilepsy
    SYMPTOMS

 and

    regression in motor skills and speech development
    SYMPTOMS

.

    Juvenile Sandhoff disease
    DIAGNOSIS

 was diagnosed on the basis of a

    decreased hexosaminidase activity in leukocytes
    BIOCHEMICAL

 and a

    homozygous HEXB gene mutation
    GENETICS

. After the

    epilepsy was controlled
    MEDICATION

, the

    clinical course remained stable for years
    SYMPTOMS

, defined by a

    mild proximal myopathy
    SYMPTOMS

 and

    stable mental retardation
    SYMPTOMS

. At

    14 years of age
    AGE

 the patient experienced a second episode with

    progressively worsening general condition
    SYMPTOMS

 with

    diminishing muscle power
    SYMPTOMS

 and

    progressive ataxia
    SYMPTOMS

. Treatment was started

    with the N-alkylated imino sugar miglustat
    MEDICATION

,

    inhibiting the glucosylceramide synthase
    BIOCHEMICAL

, an essential

    enzyme for the synthesis of glycosphingolipids
    BIOCHEMICAL

.

    Diarrhoea
    MEDICATION

 was

    treated with lactose restriction
    MEDICATION

. We performed

    detailed biochemical investigations
    PARACLINICAL

,

    motor and mental development analysis
    PARACLINICAL

,

    brain imaging
    PARACLINICAL

,

    organ function studies
    PARACLINICAL

 and

    quality of life score
    PARACLINICAL

 prior to and at different time points after start of the treatment. Two years after the initiation

    of therapy
    MEDICATION

 the patient has a

    stable neurological picture
    SYMPTOMS

    without further regression in his motor development, ataxia or intelligence
    NEG_FINDINGS

. There is a

    subjective improvement in the fine motor skills and walking up the stairs
    SYMPTOMS

 but

    no change in the quality of life score
    NEG_FINDINGS

. Under treatment with

    miglustat
    MEDICATION

 the clinical course in our patient with

    Sandhoff disease
    DIAGNOSIS

 did

    not further deteriorate
    NEG_FINDINGS

.

lysosomal storage diseases
Gaucher disease
Sandhoff disease
Juvenile Sandhoff disease
Sandhoff disease


Niemann-Pick disease, type B with TRAP-positive storage cells and secondary sea blue histiocytosis.

We present 2 cases of Niemann Pick disease, type B with secondary sea-blue histiocytosis. Strikingly, in both cases the Pick cells were positive for tartrate resistant acid phosphatase, a finding hitherto described only in Gaucher cells. This report highlights the importance of this finding as a potential cytochemical diagnostic pitfall in the diagnosis of Niemann Pick disease.

We present 2 cases of

    Niemann Pick disease, type B
    DIAGNOSIS

 with

    secondary sea-blue histiocytosis
    MICROSCOPIC

. Strikingly, in both cases

    the Pick cells were positive for tartrate resistant acid phosphatase
    MICROSCOPIC

, a finding hitherto described only in

    Gaucher cells
    MICROSCOPIC

. This report highlights the importance of this finding as a potential cytochemical diagnostic pitfall in the diagnosis of

    Niemann Pick disease
    DIAGNOSIS

.

Niemann Pick disease, type B
Niemann Pick disease


Gaucher disease with communicating hydrocephalus and cardiac involvement.

A 14-year-old female with Gaucher disease presented with hydrocephalus, corneal opacities, cirrhosis, and cardiac valvular involvement. A homozygous D409H mutation was identified. She underwent surgery for aortic and mitral valve replacement. Because of severe calcification of the aortic root, no successful valve replacement was performed. She died on the third day after the explorative cardiac surgery. Cardiac abnormalities represent a life-threatening presentation of the homozygous D409H mutation. Identification of this type is essential prior to initiating appropriate therapy with enzyme replacement and cardiac corrective surgery.

A

    14-year-old
    AGE

    female
    GENDER

 with

    Gaucher disease
    DIAGNOSIS

 presented with

    hydrocephalus
    SYMPTOMS

,

    corneal opacities
    SYMPTOMS

,

    cirrhosis
    SYMPTOMS

, and

    cardiac valvular involvement
    SYMPTOMS

. A

    homozygous D409H mutation
    GENETICS

 was identified.

    She
    GENDER

 underwent

    surgery for aortic and mitral valve replacement
    MEDICATION

. Because of

    severe calcification of the aortic root
    SYMPTOMS

,

    no successful valve replacement was performed
    NEG_FINDINGS

.

    She
    GENDER

    died
    SYMPTOMS

 on the third day after the

    explorative cardiac surgery
    MEDICATION

.

    Cardiac abnormalities
    SYMPTOMS

 represent a life-threatening presentation of the

    homozygous D409H mutation
    GENETICS

. Identification of this type is essential prior to initiating appropriate

    therapy with enzyme replacement
    MEDICATION

 and

    cardiac corrective surgery
    MEDICATION

.

hydrocephalus
corneal opacities
cirrhosis
cardiac valvular involvement
severe calcification of the aortic root
died
Cardiac abnormalities

homozygous D409H mutation
homozygous D409H mutation


Type I Gaucher disease (GDI) in three siblings: enzyme replacement treatment (ERT) required.

(Full text is available at http://www.manu.edu.mk/prilozi). This is a family of three children, born to healthy Macedonian parents after uneventful pregnancies and delivery. The index child was an eight-year-old girl admitted for abdominal discomfort and distension: the spleen was 14cm below the costal margin (BCM), the liver 8cm BCM. No bone pain or pathology was reported. There was mild pancytopaenia (hemoglobin 11.2 gm/L; WBC counts 4.6 x 10;3; platelets 70 x 10;3). Liver function tests, renal ultrasound, bone scan, and a chest radiograph were within normal limits. Bone marrow analysis in this child and her two brothers (11 and 6.5 years old) revealed Gaucher cells. Both brothers had only mild anaemia, but the older brother had been splenectomized prior to diagnosis of GD1. Enzyme analysis revealed low activity (2.59, 1.62, and 2.55 nmol/h/mg protein, respectively); plasma chitotriosidase levels were also elevated. Genetic testing revealed homozygosity for the N370S/N370S mutation in all three siblings. In the absence of available enzyme replacement treatment (ERT), the girl was splenectomized. Removing an important immune organ (the spleen) introduces further risk for the patients. In addition, this does not solve the bone involvement characteristic for GD. ERT should be introduced for all GD1 patients in Macedonia. Key words: Gaucher disease, N370S mutation, siblings, enzyme replacement therapy.

(Full text is available at http://www.manu.edu.mk/prilozi). This is a

    family of
    FAMILY

 three children, born to healthy

    Macedonian
    ETHNICITY

 parents after

    uneventful pregnancies and delivery
    MEDICATION

. The index child was an

    eight-year-old
    AGE

    girl
    GENDER

 admitted for

    abdominal discomfort
    SYMPTOMS

 and

    distension
    SYMPTOMS

: the

    spleen was 14cm below the costal margin (BCM), the liver 8cm BCM
    SYMPTOMS

.

    No bone pain or pathology was reported
    NEG_FINDINGS

. There was

    mild pancytopaenia (hemoglobin 11.2 gm/L; WBC counts 4.6 x 10;3; platelets 70 x 10;3)
    BIOCHEMICAL

.

    Liver function tests
    NEG_FINDINGS

,

    renal ultrasound
    PARACLINICAL

,

    bone scan
    PARACLINICAL

, and a

    chest radiograph were within normal limits
    NEG_FINDINGS

.

    Bone marrow analysis
    PARACLINICAL

 in this

    child
    AGE

 and

    her
    GENDER

    two brothers (11 and 6.5 years old
    FAMILY

) revealed

    Gaucher cells
    MICROSCOPIC

.

    Both brothers had only mild anaemia
    FAMILY

, but the

    older brother had been splenectomized
    FAMILY

 prior to diagnosis of

    GD1
    DIAGNOSIS

.

    Enzyme analysis
    PARACLINICAL

 revealed

    low activity (2.59, 1.62, and 2.55 nmol/h/mg protein, respectively)
    BIOCHEMICAL

;

    plasma chitotriosidase levels were also elevated
    BIOCHEMICAL

.

    Genetic testing
    PARACLINICAL

 revealed

    homozygosity for the N370S/N370S mutation in all three siblings
    FAMILY

. In the

    absence of available enzyme replacement treatment (ERT)
    NEG_FINDINGS

, the

    girl
    GENDER

 was

    splenectomized
    MEDICATION

.

    Removing an important immune organ (the spleen)
    MEDICATION

 introduces further risk for the patients. In addition, this does not solve the

    bone involvement
    SYMPTOMS

 characteristic for

    GD
    DIAGNOSIS

.

    ERT
    MEDICATION

 should be introduced for all

    GD1
    DIAGNOSIS

 patients in

    Macedonia
    ETHNICITY

. Key words:

    Gaucher disease
    DIAGNOSIS

,

    N370S mutation
    GENETICS

,

    siblings
    MEDICATION

,

    enzyme replacement therapy
    MEDICATION

.


Type 2 Gaucher disease occurs in Ashkenazi Jews but is surprisingly rare.

Patients with Gaucher disease (GD) are divided into three types based on the presence and rate of progression of the neurologic manifestations. While type 1 GD has a strong predilection in the Jewish Ashkenazi population, both other types lack such a propensity. We report the occurrence of type 2 GD (GD2) in four pregnancies in two Jewish families in Israel (in one case the mother was not Ashkenazi but was from a Sfaradi Jewish family) and also review seven additional cases of GD2 in Ashkenazi Jewish families reported in the literature. Phenotypically, GD2 in Ashkenazi Jews does not differ significantly from this form in other ethnic groups. Genotypic analysis of probands from the two Israeli families demonstrates that each carried two heterozygous glucocerebrosidase mutations. We could find no explanation why GD2 is so rare in the Jewish Ashkenazi population but we could hypothesize that homozygosity for certain Ashkenazi alleles might be lethal, leading to a lower than expected frequency of GD2 and noted that no cases of homozygous L444P has ever been described in Ashkenazi Jews.

Patients with

    Gaucher disease (GD)
    DIAGNOSIS

 are divided into three types based on the presence and rate of progression of the

    neurologic manifestations
    SYMPTOMS

. While

    type 1 GD
    DIAGNOSIS

 has a strong predilection in the

    Jewish Ashkenazi
    ETHNICITY

 population, both other types lack such a propensity. We report the occurrence of

    type 2 GD (GD2)
    DIAGNOSIS

 in four

    pregnancies
    DIAGNOSIS

 in two

    Jewish
    ETHNICITY

 families in

    Israel
    ETHNICITY

 (in one case

    the mother was not Ashkenazi but was from a Sfaradi Jewish family)
    FAMILY

 and also review seven additional cases of

    GD2
    DIAGNOSIS

 in

    Ashkenazi Jewish
    ETHNICITY

 families reported in the literature. Phenotypically,

    GD2
    DIAGNOSIS

 in

    Ashkenazi Jews
    ETHNICITY

 does not differ significantly from this form in other ethnic groups.

    Genotypic analysis
    PARACLINICAL

 of probands from the two

    Israeli
    ETHNICITY

 families demonstrates that each carried

    two heterozygous glucocerebrosidase mutations
    GENETICS

. We could find no explanation why

    GD2
    DIAGNOSIS

 is so rare in the

    Jewish Ashkenazi
    ETHNICITY

 population but we could hypothesize that

    homozygosity for certain Ashkenazi alleles might be lethal
    GENETICS

, leading to a lower than expected frequency of

    GD2
    DIAGNOSIS

 and noted that no cases of

    homozygous L444P
    GENETICS

 has ever been described in

    Ashkenazi Jews
    ETHNICITY

.

Jewish Ashkenazi
Jewish
Israel
Ashkenazi Jewish
Ashkenazi Jews
Israeli
Jewish Ashkenazi
Ashkenazi Jews


Gaucher's disease diagnosed by splenectomy.

Splenectomy continues to find common therapeutic indications for hematologic disorders. In addition, recently it is also performed in surgical clinics to assist diagnose of some illnesses. Gaucher's disease, especially Type I, is the most frequently encountered lysosomal storage disorder in man. Manifestations of it are highly variable. The most frequently found symptoms include splenomegaly with anaemia and thrombocytopenia, mostly due to hypersplenism, hepatomegaly and bone disease.

Four patients were reported in the present study. Three of them were easily diagnosed with Gaucher's disease via bone marrow cytology, and one with Gaucher's disease was detected by pathological examination following the splenectomy.

For the pouse of diagnosis of the Gaucher's disease, performing surgery is generally not necessary. However, for the cases of difficult to diagnose by classical methods, the corect diagnosis of Gaucher's disease can only be made by a special operation.

    Splenectomy
    MEDICATION

 continues to find common therapeutic indications for

    hematologic disorders
    DIAGNOSIS

. In addition, recently it is also performed in surgical clinics to assist diagnose of some illnesses.

    Gaucher's disease
    DIAGNOSIS

, especially

    Type I
    DIAGNOSIS

, is the most frequently encountered

    lysosomal storage disorder
    DIAGNOSIS

 in

    man
    GENDER

. Manifestations of it are highly variable. The most frequently found symptoms include

    splenomegaly
    SYMPTOMS

 with

    anaemia
    BIOCHEMICAL

 and

    thrombocytopenia
    BIOCHEMICAL

, mostly due to

    hypersplenism
    BIOCHEMICAL

,

    hepatomegaly
    SYMPTOMS

 and

    bone disease
    SYMPTOMS

.

Four patients were reported in the present study. Three of them were easily diagnosed with

    Gaucher's disease
    DIAGNOSIS

 via

    bone marrow cytology
    PARACLINICAL

, and one with

    Gaucher's disease
    DIAGNOSIS

 was detected by

    pathological examination
    PARACLINICAL

 following the

    splenectomy
    MEDICATION

.

For the pouse of diagnosis of the

    Gaucher's disease
    DIAGNOSIS

, performing

    surgery
    MEDICATION

 is generally not necessary. However, for the cases of difficult to diagnose by classical methods, the corect diagnosis of

    Gaucher's disease
    DIAGNOSIS

 can only be made by a special operation.

hematologic disorders
Gaucher's disease
Type I
lysosomal storage disorder
Gaucher's disease
Gaucher's disease
Gaucher's disease
Gaucher's disease


Gaucher's disease.

Gaucher's disease is the most common group of lysosomal storage disorders caused by defective activity of an enzyme beta-glucosidase leading to accumulation of glucocerebroside in cells of macrophage lineage. Accumulation of glucosylceramide in tissues leads to multisystem organ involvement viz. liver, spleen, bone marrow, lungs and central nervous system. Serum beta=glucosidase levels <15% of mean normal activity confirms the diagnosis, enzyme replacement being the only definitive treatment. We report a clinical case of a 21 year male with Gaucher's disease. To the best of our knowledge only six cases of Gaucher's disease have been reported from India so far.

    Gaucher's disease
    DIAGNOSIS

 is the most common group of

    lysosomal storage disorders
    DIAGNOSIS

 caused by

    defective activity of an enzyme beta-glucosidase
    BIOCHEMICAL

 leading to

    accumulation of glucocerebroside in cells of macrophage lineage
    MICROSCOPIC

.

    Accumulation of glucosylceramide in tissues
    MICROSCOPIC

 leads to

    multisystem organ involvement
    MICROSCOPIC

    viz. liver, spleen, bone marrow, lungs and central nervous system
    MICROSCOPIC

.

    Serum beta=glucosidase levels <15% of mean normal activity
    BIOCHEMICAL

 confirms the diagnosis,

    enzyme replacement
    MEDICATION

 being the only definitive treatment. We report a clinical case of a

    21 year male
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

. To the best of our knowledge only six cases of

    Gaucher's disease
    DIAGNOSIS

 have been reported from

    India
    ETHNICITY

 so far.

Gaucher's disease
lysosomal storage disorders
Gaucher's disease
Gaucher's disease


A patient with parkinsonism related to Gaucher's disease type I successfully treated by unilateral pallidotomy - a 3-year follow-up.

Gaucher's disease is the most common hereditary lysosomal storage disorder and presents with a wide clinical spectrum including parkinsonism. We present a patient first diagnosed with idiopathic Parkinson's disease at the age of 38 due to left-sided bradykinesia and rigidity. But thereafter the diagnosis of Gaucher's disease type I according to clinical pictures and clinical genetic testing was made. Despite the optimal enzyme replacement therapy, the parkinsonian symptoms worsened. He was referred for consideration for surgical treatment of his severe parkinsonism. At the age of 54 he underwent right-sided posteroventrolateral pallidotomy. The surgery was uneventful and he immediately improved. On the last examination performed 3 years later, he had mild parkinsonism and was independent in all activities of daily living. This case demonstrates a benefit of surgical treatment for genetically proven Gaucher's disease type I.

    Gaucher's disease
    DIAGNOSIS

 is the most common

    hereditary
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 and presents with a wide clinical spectrum including

    parkinsonism
    DIAGNOSIS

. We present a patient first diagnosed with

    idiopathic Parkinson's disease
    DIAGNOSIS

 at the

    age of 38
    AGE

 due to

    left-sided bradykinesia and rigidity
    SYMPTOMS

. But thereafter the diagnosis of

    Gaucher's disease type I
    DIAGNOSIS

 according to clinical pictures and

    clinical genetic testing
    PARACLINICAL

 was made.

    Despite the optimal enzyme replacement therapy
    NEG_FINDINGS

, the

    parkinsonian symptoms worsened
    SYMPTOMS

.

    He
    GENDER

 was referred for consideration for

    surgical treatment
    MEDICATION

 of his

    severe parkinsonism
    DIAGNOSIS

. At the

    age of 54
    AGE

 he underwent

    right-sided posteroventrolateral pallidotomy
    MEDICATION

. The

    surgery was uneventful
    MEDICATION

 and he

    immediately improved
    SYMPTOMS

. On the last examination performed 3 years later,

    he
    GENDER

 had

    mild parkinsonism
    SYMPTOMS

 and was

    independent in all activities of daily living
    NEG_FINDINGS

. This case demonstrates a benefit of

    surgical treatment
    MEDICATION

 for genetically proven Gaucher's disease type I.

Gaucher's disease
lysosomal storage disorder
parkinsonism
idiopathic Parkinson's disease
Gaucher's disease type I
severe parkinsonism

left-sided bradykinesia and rigidity
parkinsonian symptoms worsened
immediately improved
mild parkinsonism


[Cerebellar syndrome in Gaucher's disease].

This is a report on a 37-year-old female patient with enzymatically verified Gaucher's disease. The clinical symptoms corresponded to the neuronopathic form of the disease (type 3). A progressive cerebellar syndrome had been developing for 1 year. So far, there have been no records of complex cerebellar symptoms in connection with Gaucher's disease in the literature. After ruling out other differential diagnoses Gaucher's disease was considered to be the cause of such cerebellar symptoms, which could be attributed to toxic glucocerebroside deposits in the cerebellum.

This is a report on a

    37-year-old
    AGE

    female
    GENDER

 patient with enzymatically verified

    Gaucher's disease
    DIAGNOSIS

. The clinical symptoms corresponded to the

    neuronopathic form of the disease (type 3)
    DIAGNOSIS

. A

    progressive cerebellar syndrome
    SYMPTOMS

 had been developing for 1 year. So far, there have been no records of

    complex cerebellar symptoms
    SYMPTOMS

 in connection with

    Gaucher's disease
    DIAGNOSIS

 in the literature. After

    ruling out other differential diagnoses
    NEG_FINDINGS

    Gaucher's disease
    DIAGNOSIS

 was considered to be the cause of such

    cerebellar symptoms
    SYMPTOMS

, which could be attributed to

    toxic glucocerebroside deposits in the cerebellum
    MICROSCOPIC

.

progressive cerebellar syndrome
complex cerebellar symptoms
cerebellar symptoms


Gaucher's disease with uncommon presentations.

Gaucher's disease is the most common lysosomal storage disorder gene defect, which leads to deficiency or decreased activity of glucocerebrosidase, followed by accumulation of glucosylceramide. There is autosomal recessive transmission leading to varied clinical manifestations. This disease has three main types: Type I - nonneuronopathic; type II - acute neuronopathic; and type III - chronic neuronopathic. The nonneuronopathic type has the highest prevalence and also the greatest variability. The authors here report two cases of Gaucher's disease with uncommon presentations in early childhood, highlighting the importance of early diagnosis of the disease, as now-a-days enzyme replacement therapy may arrest further progress of disease.

    Gaucher's disease
    DIAGNOSIS

 is the most common

    lysosomal storage disorder
    DIAGNOSIS

    gene defect
    GENETICS

, which leads to

    deficiency or decreased activity of glucocerebrosidase
    BIOCHEMICAL

, followed by

    accumulation of glucosylceramide
    MICROSCOPIC

. There is

    autosomal recessive transmission
    GENETICS

 leading to varied clinical manifestations. This disease has three main types:

    Type I - nonneuronopathic
    DIAGNOSIS

;

    type II - acute neuronopathic
    DIAGNOSIS

; and

    type III - chronic neuronopathic
    DIAGNOSIS

. The

    nonneuronopathic type
    DIAGNOSIS

 has the highest prevalence and also the greatest variability. The authors here report two cases of

    Gaucher's disease
    DIAGNOSIS

 with uncommon presentations in

    early childhood
    AGE

, highlighting the importance of early diagnosis of the disease, as now-a-days

    enzyme replacement therapy
    MEDICATION

 may arrest further progress of disease.

Gaucher's disease
lysosomal storage disorder
Type I - nonneuronopathic
type II - acute neuronopathic
type III - chronic neuronopathic
nonneuronopathic type
Gaucher's disease

gene defect
autosomal recessive transmission


IgM monoclonal component associated with type I Gaucher disease resolved after enzyme replacement therapy: a case report.

The frequency of monoclonal gammopathy of undetermined significance (MGUS) is higher in patients with type I Gaucher disease (GD I) than in the general population. Although enzyme replacement therapy is effective in the control of the disease, its effect on MGUS is still controversial. We present the case of a 65-year-old woman with extensive GD I associated with IgM MGUS, in whom enzyme replacement therapy succeeded in eradicating the monoclonal component. This observation further supports the idea that enzyme replacement therapy decreases the chronic antigenic stimulation responsible for gammopathies in Gaucher disease.

The frequency of

    monoclonal gammopathy of undetermined significance (MGUS)
    DIAGNOSIS

 is higher in patients with

    type I Gaucher disease (GD I)
    DIAGNOSIS

 than in the general population. Although

    enzyme replacement therapy
    MEDICATION

 is effective in the control of the disease, its effect on

    MGUS
    DIAGNOSIS

 is still controversial. We present the case of a

    65-year-old
    AGE

    woman
    GENDER

 with

    extensive GD I
    DIAGNOSIS

 associated with

    IgM MGUS
    DIAGNOSIS

, in whom

    enzyme replacement therapy
    MEDICATION

 succeeded in

    eradicating the monoclonal component
    BIOCHEMICAL

. This observation further supports the idea that

    enzyme replacement therapy
    MEDICATION

 decreases the

    chronic antigenic stimulation
    SYMPTOMS

 responsible for

    gammopathies
    BIOCHEMICAL

 in

    Gaucher disease
    DIAGNOSIS

.

enzyme replacement therapy
enzyme replacement therapy
enzyme replacement therapy

eradicating the monoclonal component
gammopathies