Improvement In Symptoms Of Gaucher's Disease By Enzyme Replacement Therapy.

Gaucher's disease is the most common lysosomal storage disease which occurs due to a deficiency of the enzyme glucocerebrosidase. This enzyme deficiency leads to accumulation of glucocerebrosidase in the cells of macrophage-monocyte system. It is inherited as an autosomal recessive mutation and has three clinical subtypes. The disease presents with anaemia, hepatosplenomegaly, skeletal disorders and organ dysfunction. We present the case of an 18- month old male child who had presented to Civil Hospital, Karachi with fever, progressive pallor, abdominal distention for 6 months and was diagnosed as a case of type 1 Gaucher's disease on the basis of low leukocyte glucocerebrosidase activity, raised plasma chitotriosidase and the presence of Gaucher cells on bone marrow biopsy. The disease was treated with Intravenous replacement of the enzyme Imiglucerase (cerezyme) and the patient was followed. An informed Consent of the parents was taken prior to the writing of the manuscript.

    Gaucher's disease
    DIAGNOSIS

 is the most common

    lysosomal storage disease
    DIAGNOSIS

 which occurs due to a

    deficiency of the enzyme glucocerebrosidase
    BIOCHEMICAL

. This

    enzyme deficiency
    BIOCHEMICAL

 leads to

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

. It is

    inherited as an autosomal recessive mutation
    GENETICS

 and has three clinical subtypes. The disease presents with

    anaemia
    BIOCHEMICAL

,

    hepatosplenomegaly
    SYMPTOMS

,

    skeletal disorders
    SYMPTOMS

 and

    organ dysfunction
    SYMPTOMS

. We present the case of an

    18- month old
    AGE

    male
    GENDER

    child
    AGE

 who had presented to Civil Hospital, Karachi with

    fever
    SYMPTOMS

,

    progressive pallor
    SYMPTOMS

,

    abdominal distention for 6 months
    SYMPTOMS

 and was diagnosed as a case of

    type 1 Gaucher's disease
    DIAGNOSIS

 on the basis of

    low leukocyte glucocerebrosidase activity
    BIOCHEMICAL

,

    raised plasma chitotriosidase
    BIOCHEMICAL

 and the

    presence of Gaucher cells on bone marrow biopsy
    MICROSCOPIC

. The disease was treated with

    Intravenous replacement of the enzyme Imiglucerase (cerezyme)
    MEDICATION

 and the patient was followed. An informed Consent of the parents was taken prior to the writing of the manuscript.

Gaucher's disease
lysosomal storage disease
type 1 Gaucher's disease

hepatosplenomegaly
skeletal disorders
organ dysfunction
fever
progressive pallor
abdominal distention for 6 months


Three mutations of adult type 1 Gaucher disease found in a Chinese patient: A case report.

Gaucher disease (GD), characterized by glucosylceramide accumulation in the macrophage-monocyte system, is caused by glucosidase b acid (GBA) gene mutations which lead to the deficiency of lysosomal enzyme glucocerebrosidase. The mutation spectrum of GBA in Chinese patients is quite different from those seen in Jewish and non-Jewish Caucasian patients. Thus, it is relatively hard to diagnose GD in Chinese.

A 24-year-old Chinese female with intermittent abdominal distension and progressive decrease in strength but without neurologic symptoms was initially referred for femoral head necrosis on the right feet. Laboratory examinations results indicated panhematopenia. Bone marrow aspiration smear and biopsy specimen found typical "wrinkled" Gaucher cells. Molecular-genetic testing of GBA gene revealed 3 mutations including R159W (c. 475 C > T), V1230G (c. 689T > G), and G241A (c. 721G > A).

On the basis of these findings and clinical manifestations, the final diagnosis of type 1 GD was made.

Enzyme replacement therapy (ERT) with velaglucerase α was carried out after the diagnosis of type 1 GD.

The platelet and hemoglobin levels were restored by ERT.

To our knowledge, this is the first report of GD patient carrying 3 mutations in Chinese. These mutations in GBA in the present case imply a potential pool of patients with GD with this mutation in Chinese.

    Gaucher disease (GD)
    DIAGNOSIS

, characterized by

    glucosylceramide accumulation in the macrophage-monocyte system
    MICROSCOPIC

, is caused by

    glucosidase b acid (GBA) gene mutations
    GENETICS

 which lead to the

    deficiency of lysosomal enzyme glucocerebrosidase
    BIOCHEMICAL

. The

    mutation spectrum of GBA
    GENETICS

 in

    Chinese
    ETHNICITY

 patients is quite different from those seen in

    Jewish
    ETHNICITY

 and

    non-Jewish Caucasian
    ETHNICITY

 patients. Thus, it is relatively hard to diagnose

    GD
    DIAGNOSIS

 in

    Chinese
    ETHNICITY

.

A

    24-year-old
    AGE

    Chinese
    ETHNICITY

    female
    GENDER

 with

    intermittent abdominal distension
    SYMPTOMS

 and

    progressive decrease in strength
    SYMPTOMS

 but

    without neurologic symptoms
    NEG_FINDINGS

 was initially referred for

    femoral head necrosis on the right feet
    SYMPTOMS

.

    Laboratory examinations
    PARACLINICAL

 results indicated

    panhematopenia
    BIOCHEMICAL

.

    Bone marrow aspiration smear
    PARACLINICAL

 and

    biopsy specimen
    PARACLINICAL

 found

    typical "wrinkled" Gaucher cells
    MICROSCOPIC

.

    Molecular-genetic testing of GBA gene
    PARACLINICAL

 revealed

    3 mutations including R159W (c. 475 C > T), V1230G (c. 689T > G), and G241A (c. 721G > A)
    GENETICS

.

On the basis of these findings and clinical manifestations, the final diagnosis of

    type 1 GD
    DIAGNOSIS

 was made.

    Enzyme replacement therapy (ERT) with velaglucerase α
    MEDICATION

 was carried out after the diagnosis of

    type 1 GD
    DIAGNOSIS

.

    The platelet and hemoglobin levels were restored
    BIOCHEMICAL

 by

    ERT
    MEDICATION

.

To our knowledge, this is the first report of

    GD
    DIAGNOSIS

 patient carrying

    3 mutations
    GENETICS

 in

    Chinese
    ETHNICITY

. These

    mutations in GBA
    GENETICS

 in the present case imply a potential pool of patients with

    GD
    DIAGNOSIS

 with this mutation in

    Chinese
    ETHNICITY

.

Gaucher disease (GD)
GD
type 1 GD
type 1 GD
GD
GD

Chinese
Jewish
non-Jewish Caucasian
Chinese
Chinese
Chinese
Chinese

intermittent abdominal distension
progressive decrease in strength
femoral head necrosis on the right feet


Neuronopathic Gaucher disease presenting with microcytic hypochromic anemia.

Gaucher disease (GD) is caused by a hereditary deficiency of glucocerebrosidase, resulting in accumulation of glucosylceramide and potentially manifesting as hepatosplenomegaly. We report the case of a 15-month-old boy with chronic neuronopathic GD. The patient had prolonged anemia despite continued iron supplementation for 3 months. White blood count (WBC), hemoglobin (Hb), platelet count, and corrected reticulocyte count were 3,300 /µL, 8.7 g/dL, 90,000 /µL, and 0.55, respectively. The patient had microcytic hypochromic anemia with mildly elevated ferritin. Physical examination revealed hepatosplenomegaly. Bone-marrow aspiration showed sheets of Gaucher cells. Glucocerebrosidase activity in monocytes was significantly lower than normal. Genetic analysis revealed a homozygous L444P mutation of GBA, and he was diagnosed with type 1 GD. Enzyme replacement treatment (ERT) consisting of imiglucerase was initiated and was effective; WBC, Hb, and platelet count gradually normalized and the hepatosplenomegaly improved. However, when the patient entered elementary school, he showed mild impaired cognitive function, and supranuclear gaze palsy occurred the same year. He was ultimately diagnosed with type 3 GD and continued ERT. Pediatric hemato-oncologists should be aware of GD, especially when patients exhibit anemia refractory to iron therapy, radiologic bone deformity, neurologic signs or symptoms, and growth retardation.

    Gaucher disease (GD)
    DIAGNOSIS

 is caused by a

    hereditary
    GENETICS

    deficiency of glucocerebrosidase
    BIOCHEMICAL

, resulting in

    accumulation of glucosylceramide
    MICROSCOPIC

 and potentially manifesting as

    hepatosplenomegaly
    SYMPTOMS

. We report the case of a

    15-month-old
    AGE

    boy
    GENDER

 with

    chronic neuronopathic GD
    DIAGNOSIS

. The patient had

    prolonged anemia
    BIOCHEMICAL

    despite continued iron supplementation for 3 months
    NEG_FINDINGS

.

    White blood count (WBC), hemoglobin (Hb), platelet count, and corrected reticulocyte count were 3,300 /µL, 8.7 g/dL, 90,000 /µL, and 0.55, respectively
    BIOCHEMICAL

. The patient had

    microcytic hypochromic anemia
    BIOCHEMICAL

 with

    mildly elevated ferritin
    BIOCHEMICAL

.

    Physical examination
    PARACLINICAL

 revealed

    hepatosplenomegaly
    SYMPTOMS

.

    Bone-marrow aspiration
    PARACLINICAL

 showed

    sheets of Gaucher cells
    MICROSCOPIC

.

    Glucocerebrosidase activity in monocytes was significantly lower than normal
    BIOCHEMICAL

.

    Genetic analysis
    PARACLINICAL

 revealed a

    homozygous L444P mutation of GBA
    GENETICS

, and

    he
    GENDER

 was diagnosed with

    type 1 GD
    DIAGNOSIS

.

    Enzyme replacement treatment (ERT) consisting of imiglucerase
    MEDICATION

 was initiated and was effective;

    WBC, Hb, and platelet count gradually normalized
    BIOCHEMICAL

 and the

    hepatosplenomegaly improved
    SYMPTOMS

. However, when the patient entered elementary school, he showed

    mild impaired cognitive function
    SYMPTOMS

, and

    supranuclear gaze palsy
    SYMPTOMS

 occurred the same year.

    He
    GENDER

 was ultimately diagnosed with

    type 3 GD
    DIAGNOSIS

 and continued

    ERT
    MEDICATION

.

    Pediatric hemato-oncologists
    PARACLINICAL

 should be aware of

    GD
    DIAGNOSIS

, especially when patients exhibit

    anemia refractory to iron therapy
    NEG_FINDINGS

,

    radiologic bone deformity
    SYMPTOMS

,

    neurologic signs or symptoms
    SYMPTOMS

, and

    growth retardation
    SYMPTOMS

.

Gaucher disease (GD)
chronic neuronopathic GD
type 1 GD
type 3 GD
GD

hereditary
homozygous L444P mutation of GBA

hepatosplenomegaly
hepatosplenomegaly
hepatosplenomegaly improved
mild impaired cognitive function
supranuclear gaze palsy
radiologic bone deformity
neurologic signs or symptoms
growth retardation


Bone manifestations in neuronopathic Gaucher disease while receiving high-dose enzyme replacement therapy.

Avascular necrosis (AVN), one type of bone infarction, is a major irreversible complication of Gaucher disease (GD). In this report, two pediatric patients with GD type 3, homozygous for the L483P pathogenic variant (formerly L444P), developed AVN despite treatment on long-term, high-dose enzyme replacement therapy (ERT). ERT was initiated in both patients, who had intact spleens, shortly after diagnosis with an initial dramatic response. However, both patients exhibited AVN after 5.5 and 11 years on high-dose ERT, respectively, despite good compliance and normalized hematological findings and visceral symptoms. This report demonstrates the importance of careful, regular surveillance of the musculoskeletal system in addition to monitoring the neurological symptoms associated with neuronopathic GD. Additionally, it highlights the limitations of ERT in terms of targeting certain sanctuary sites such as bone marrow and suggests the need for new treatment modalities other than ERT monotherapy to address these limitations.

    Avascular necrosis (AVN)
    DIAGNOSIS

, one type of

    bone infarction
    SYMPTOMS

, is a major irreversible complication of

    Gaucher disease (GD)
    DIAGNOSIS

. In this report, two

    pediatric
    AGE

 patients with

    GD type 3
    DIAGNOSIS

,

    homozygous for the L483P pathogenic variant (formerly L444P)
    GENETICS

, developed

    AVN
    DIAGNOSIS

    despite treatment on long-term, high-dose enzyme replacement therapy (ERT)
    NEG_FINDINGS

.

    ERT
    MEDICATION

 was initiated in both patients, who had

    intact spleens
    NEG_FINDINGS

, shortly after diagnosis with an initial dramatic response. However, both patients exhibited

    AVN
    DIAGNOSIS

 after 5.5 and

    11 years on high-dose ERT
    MEDICATION

, respectively,

    despite good compliance
    NEG_FINDINGS

 and

    normalized hematological findings and visceral symptoms
    NEG_FINDINGS

. This report demonstrates the importance of careful,

    regular surveillance of the musculoskeletal system
    PARACLINICAL

 in addition to monitoring the

    neurological symptoms
    SYMPTOMS

 associated with

    neuronopathic GD
    DIAGNOSIS

. Additionally, it highlights the

    limitations of ERT
    NEG_FINDINGS

 in terms of targeting certain sanctuary sites such as bone marrow and suggests the need for new treatment modalities other than

    ERT monotherapy
    MEDICATION

 to address these limitations.

Avascular necrosis (AVN)
Gaucher disease (GD)
GD type 3
AVN
AVN
neuronopathic GD

ERT
11 years on high-dose ERT
ERT monotherapy


Aortic calcification in Gaucher disease: a case report.

Gaucher disease is the most common sphingolipid storage disease and is present in all ethnic groups. Its symptoms span all systems including the cardiovascular system. The health care provider should be vigilant regarding this potentially fatal complication. Gaucher disease type IIIC has been linked to causing oculomotor apraxia and cardiac calcification. We report a Saudi girl who developed valvular and aortic calcification in late childhood and died as a result of her cardiovascular complications. This report further strengthens the association and reminds the clinicians that patients with D409H mutation need echocardiographic evaluation annually.

    Gaucher disease
    DIAGNOSIS

 is the most common

    sphingolipid storage disease
    DIAGNOSIS

 and is present in all ethnic groups. Its

    symptoms span all systems including the cardiovascular system
    SYMPTOMS

. The health care provider should be vigilant regarding this potentially fatal complication.

    Gaucher disease type IIIC
    DIAGNOSIS

 has been linked to causing

    oculomotor apraxia
    SYMPTOMS

 and

    cardiac calcification
    SYMPTOMS

. We report a

    Saudi
    ETHNICITY

    girl
    GENDER

 who developed

    valvular and aortic calcification
    SYMPTOMS

 in

    late childhood
    AGE

 and

    died
    SYMPTOMS

 as a result of

    her
    GENDER

    cardiovascular complications
    SYMPTOMS

. This report further strengthens the association and reminds the clinicians that patients with

    D409H mutation
    GENETICS

 need

    echocardiographic evaluation
    PARACLINICAL

 annually.

Gaucher disease
sphingolipid storage disease
Gaucher disease type IIIC


Progressive myoclonus epilepsy in Gaucher Disease due to a new Gly-Gly mutation causing loss of an Exonic Splicing Enhancer.

Patients with Gaucher Disease (GD) exhibit three phenotypes, including type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic).

Identifying which GBA changes represent benign polymorphisms and which may result in disease-causing mutations is essential for diagnosis and genotype/phenotype correlations but is often challenging.

Here, we describe a patient with type 3 GD, presenting with drug-resistant epilepsy, who bears a set of GBA polymorphic variants including the novel c.363A > G (Gly82Gly) synonymous mutation. In silico predictions, mRNA and functional studies revealed that the new Gly82Gly mutation causes skipping of GBA exon 4, leading to a severe reduction of the wild type GBA mRNA. This is the first report of a synonymous change causing GD through loss of an exonic splicing enhancer sequence. The synonymous mutation is in trans with the Asn188Ser missense mutation, thus making the Asn188Ser responsible for the patient's phenotype and strengthening the association of Asn188Ser with the particular neurological phenotype of type 3 GD.

We strengthen the association of Asn188Ser with the type 3 GD phenotype and progressive myoclonus epilepsy. Our data confirm that in silico predictions and mRNA analysis are mandatory in discriminating pathological mutations from the background of harmless polymorphisms, especially synonymous changes.

Patients with

    Gaucher Disease (GD)
    DIAGNOSIS

 exhibit three phenotypes, including

    type 1 (non-neuronopathic)
    DIAGNOSIS

,

    type 2 (acute neuronopathic)
    DIAGNOSIS

, and

    type 3 (subacute neuronopathic)
    DIAGNOSIS

.

Identifying which

    GBA changes represent benign polymorphisms
    GENETICS

 and which may

    result in disease-causing mutations
    GENETICS

 is essential for diagnosis and genotype/phenotype correlations but is often challenging.

Here, we describe a patient with

    type 3 GD
    DIAGNOSIS

, presenting with

    drug-resistant epilepsy
    NEG_FINDINGS

, who bears a set of

    GBA polymorphic variants
    GENETICS

 including the

    novel c.363A > G (Gly82Gly) synonymous mutation
    GENETICS

.

    In silico predictions, mRNA and functional studies
    PARACLINICAL

 revealed that the

    new Gly82Gly mutation causes skipping of GBA exon 4, leading to a severe reduction of the wild type GBA mRNA
    GENETICS

. This is the first report of a

    synonymous change
    GENETICS

 causing

    GD
    DIAGNOSIS

 through

    loss of an exonic splicing enhancer sequence
    GENETICS

.

    The synonymous mutation is in trans with the Asn188Ser missense mutation, thus making the Asn188Ser responsible for the
    GENETICS

 patient's phenotype and strengthening the

    association of Asn188Ser with the particular neurological phenotype
    GENETICS

 of

    type 3 GD
    DIAGNOSIS

.

We strengthen the association of

    Asn188Ser
    GENETICS

 with the

    type 3 GD phenotype
    DIAGNOSIS

 and

    progressive myoclonus epilepsy
    SYMPTOMS

. Our data confirm that

    in silico predictions
    PARACLINICAL

 and

    mRNA analysis
    PARACLINICAL

 are mandatory in discriminating

    pathological mutations
    GENETICS

 from the background of

    harmless polymorphisms, especially synonymous changes
    GENETICS

.

Gaucher Disease (GD)
type 1 (non-neuronopathic)
type 2 (acute neuronopathic)
type 3 (subacute neuronopathic)
type 3 GD
GD
type 3 GD
type 3 GD phenotype


Corticobasal syndrome in a man with Gaucher disease type 1: Expansion of the understanding of the neurological spectrum.

Gaucher disease (GD) is an autosomal recessive condition that results from a deficiency of the enzyme β-glucocerebrosidase. The increased risk of primary parkinsonism symptoms among individuals affected with GD and carriers for the disorder is well-documented in the literature. However, these risks and case reports often reflect patients with classical Parkinson's disease (PD) symptoms. We report a patient with GD type 1 who was diagnosed with corticobasal syndrome (CBS), a clinical atypical parkinsonism diagnosis, in his sixth decade of life. Our case highlights the need to consider forms of atypical parkinsonism such as CBS in addition to PD in the differential diagnosis of cognitive and motor changes in patients with GD type 1. We also recommend careful assessment and routine monitoring of cognition, mood, behavior, sleep patterns, olfaction, and memory in patients with GD type 1 to identify early symptoms indicative of neurological involvement.

    Gaucher disease (GD)
    DIAGNOSIS

 is an

    autosomal recessive
    GENETICS

 condition that results from a

    deficiency of the enzyme β-glucocerebrosidase
    BIOCHEMICAL

. The increased risk of

    primary parkinsonism symptoms
    SYMPTOMS

 among individuals affected with

    GD
    DIAGNOSIS

 and carriers for the disorder is well-documented in the literature. However, these risks and case reports often reflect patients with

    classical Parkinson's disease (PD) symptoms
    SYMPTOMS

. We report a patient with

    GD type 1
    DIAGNOSIS

 who was diagnosed with

    corticobasal syndrome (CBS)
    DIAGNOSIS

, a clinical

    atypical parkinsonism diagnosis
    DIAGNOSIS

, in

    his
    GENDER

    sixth decade of life
    AGE

. Our case highlights the need to consider forms of

    atypical parkinsonism
    DIAGNOSIS

 such as

    CBS
    DIAGNOSIS

 in addition to

    PD
    DIAGNOSIS

 in the

    differential diagnosis
    PARACLINICAL

 of

    cognitive and motor changes
    SYMPTOMS

 in patients with

    GD type 1
    DIAGNOSIS

. We also recommend

    careful assessment and routine monitoring of cognition, mood, behavior, sleep patterns, olfaction, and memory
    PARACLINICAL

 in patients with

    GD type 1
    DIAGNOSIS

 to identify

    early symptoms indicative of neurological involvement
    SYMPTOMS

.

Gaucher disease (GD)
GD
GD type 1
corticobasal syndrome (CBS)
atypical parkinsonism diagnosis
atypical parkinsonism
CBS
PD
GD type 1
GD type 1


Fever, pulmonary interstitial fibrosis, and hepatomegaly in a 15-year-old boy with Gaucher disease: a case report.

Gaucher disease is an autosomal recessive disorder resulting from the accumulation of glucocerebroside in the cells of the macrophage-monocyte system caused by deficiency in lysosomal glucocerebrosidase. Intravenously administered enzyme replacement therapy is the first-line therapy for Gaucher disease type 1 and substrate reduction therapy represents an alternative oral treatment. Here is a rare case report of Gaucher disease in South China.

Our patient was a 15-year-old Han Chinese boy presenting with fever, edema, and gradually increasing abdominal girth. A physical examination revealed obvious hypoevolutism and hepatomegaly, and laboratory tests and imaging examinations showed severe pulmonary interstitial fibrosis, infection, and moderate anemia. A final diagnosis of Gaucher disease was confirmed after examining the splenic pathological section derived from a splenectomy performed 6 years ago. His recovery improved after receiving anti-infection, diuresis, blood transfusion, and hepatoprotection and so on. However, enzyme replacement therapy was not adopted by our patient because his family could not afford it.

A rare case of Gaucher disease is reported here to emphasize the importance of early recognition by clinical manifestation and histological findings. Gaucher disease should be considered in the differential diagnosis of children with unexplained symptoms of multiple systems.

    Gaucher disease
    DIAGNOSIS

 is an

    autosomal recessive disorder
    GENETICS

 resulting from the

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

 caused by

    deficiency in lysosomal glucocerebrosidase
    BIOCHEMICAL

.

    Intravenously administered enzyme replacement therapy
    MEDICATION

 is the first-line therapy for

    Gaucher disease type 1
    DIAGNOSIS

 and

    substrate reduction therapy
    MEDICATION

 represents an

    alternative oral treatment
    MEDICATION

. Here is a rare case report of

    Gaucher disease
    DIAGNOSIS

 in

    South China
    ETHNICITY

.

Our patient was a

    15-year-old
    AGE

    Han Chinese
    ETHNICITY

    boy
    GENDER

 presenting with

    fever
    SYMPTOMS

,

    edema
    SYMPTOMS

, and

    gradually increasing abdominal girth
    SYMPTOMS

. A

    physical examination
    PARACLINICAL

 revealed obvious

    hypoevolutism
    SYMPTOMS

 and

    hepatomegaly
    SYMPTOMS

, and

    laboratory tests
    PARACLINICAL

 and

    imaging examinations
    PARACLINICAL

 showed

    severe pulmonary interstitial fibrosis
    MICROSCOPIC

,

    infection
    SYMPTOMS

, and

    moderate anemia
    BIOCHEMICAL

. A final diagnosis of

    Gaucher disease
    DIAGNOSIS

 was confirmed after

    examining the splenic pathological section
    PARACLINICAL

 derived from a

    splenectomy
    MEDICATION

 performed 6 years ago. His recovery improved after

    receiving anti-infection, diuresis, blood transfusion, and hepatoprotection
    MEDICATION

 and so on. However,

    enzyme replacement therapy was not adopted
    NEG_FINDINGS

 by our patient because

    his
    GENDER

    family could not afford it
    FAMILY

.

A rare case of

    Gaucher disease
    DIAGNOSIS

 is reported here to emphasize the importance of early recognition by clinical manifestation and

    histological findings
    PARACLINICAL

.

    Gaucher disease
    DIAGNOSIS

 should be considered in the

    differential diagnosis
    PARACLINICAL

 of

    children
    AGE

 with

    unexplained symptoms of multiple systems
    SYMPTOMS

.

Gaucher disease
Gaucher disease type 1
Gaucher disease
Gaucher disease
Gaucher disease
Gaucher disease


Thalamic and dentate nucleus abnormalities in the brain of children with Gaucher disease.

Gaucher disease (GD) represents the most common lysosomal storage defect. It is classified into three phenotypes: type 1 non-neuronopathic, type 2 acute neuronopathic, and type 3 subacute/chronic neuronopathic. Although children affected by GD may present with a broad spectrum of neurological signs, brain magnetic resonance imaging (MRI) findings are usually normal or non-specific. We report three cases of GD with previously undescribed brain MRI changes mainly affecting the thalami and/or the dentate nuclei. We discuss the possible etiopathogenesis of these abnormalities. Correlation between brain MRI abnormalities, neurological symptoms, and treatment efficacy is still unclear.

    Gaucher disease (GD)
    DIAGNOSIS

 represents the most common

    lysosomal storage defect
    DIAGNOSIS

. It is classified into three phenotypes:

    type 1 non-neuronopathic
    DIAGNOSIS

,

    type 2 acute neuronopathic
    DIAGNOSIS

, and

    type 3 subacute/chronic neuronopathic
    DIAGNOSIS

. Although

    children
    AGE

 affected by

    GD
    DIAGNOSIS

 may present with a

    broad spectrum of neurological signs
    SYMPTOMS

,

    brain magnetic resonance imaging (MRI) findings are usually normal or non-specific
    NEG_FINDINGS

. We report three cases of

    GD
    DIAGNOSIS

 with

    previously undescribed brain MRI changes mainly affecting the thalami and/or the dentate nuclei
    SYMPTOMS

. We discuss the possible etiopathogenesis of these abnormalities. Correlation between

    brain MRI abnormalities
    SYMPTOMS

,

    neurological symptoms
    SYMPTOMS

, and treatment efficacy is still unclear.

Gaucher disease (GD)
lysosomal storage defect
type 1 non-neuronopathic
type 2 acute neuronopathic
type 3 subacute/chronic neuronopathic
GD
GD


Enzyme Replacement Therapy in a Gaucher Family.

Gaucher disease is a lipid storage disorder due to deficiency of beta glucocerebrosidase. It's an autosomal recessive disease and as a result of this enzyme deficiency, glucocerebroside accumulates in various types of tissues like liver, brain spleen and bone marrow. We aimed to describe the effects of enzyme replacement therapy in three members of a family with Gaucher disease and to emphasize screening of the family members of the patients with Gaucher disease. Furthermore, late diagnosis and treatment in these patients have a minimal effect on improvement of the quality of life, and early diagnosis and treatment are very important in Gaucher disease.

    Gaucher disease
    DIAGNOSIS

 is a

    lipid storage disorder
    DIAGNOSIS

 due to

    deficiency of beta glucocerebrosidase
    BIOCHEMICAL

. It's an

    autosomal recessive disease
    GENETICS

 and as a result of this

    enzyme deficiency
    BIOCHEMICAL

,

    glucocerebroside accumulates in various types of tissues like liver, brain spleen and bone marrow
    MICROSCOPIC

. We aimed to describe the effects of

    enzyme replacement therapy
    MEDICATION

 in three members of a

    family with Gaucher disease
    FAMILY

 and to emphasize screening of the family members of the patients with

    Gaucher disease
    DIAGNOSIS

. Furthermore, late diagnosis and treatment in these patients have a minimal effect on improvement of the quality of life, and early diagnosis and treatment are very important in

    Gaucher disease
    DIAGNOSIS

.

Gaucher disease
lipid storage disorder
Gaucher disease
Gaucher disease

deficiency of beta glucocerebrosidase
enzyme deficiency


Cauda equina syndrome in a patient diagnosed with type 1 Gaucher disease: a rare case.

Gaucher disease is a rare hereditary glycolipid storage disease. One of the rare complications is neurodeficits due to vertebral involvement.

An 18-year-old female patient presented to the outpatient clinic with cauda equina syndrome due to sacral involvement of type 1 GD. Bilateral laminectomy via posterior approach without posterior stabilization was performed.

Maximum excision of the mass avoiding destabilization of the spinal column can provide long-term vertebral stability and improvement in neurodeficits.

    Gaucher disease
    DIAGNOSIS

 is a

    rare hereditary
    GENETICS

    glycolipid storage disease
    DIAGNOSIS

. One of the rare complications is

    neurodeficits due to vertebral involvement
    SYMPTOMS

.

An

    18-year-old
    AGE

    female
    GENDER

 patient presented to the outpatient clinic with

    cauda equina syndrome
    DIAGNOSIS

 due to

    sacral involvement
    SYMPTOMS

 of

    type 1 GD
    DIAGNOSIS

.

    Bilateral laminectomy via posterior approach without posterior stabilization
    MEDICATION

 was performed.

    Maximum excision of the mass avoiding destabilization of the spinal column
    MEDICATION

 can provide

    long-term vertebral stability
    SYMPTOMS

 and

    improvement in neurodeficits
    SYMPTOMS

.

Gaucher disease
glycolipid storage disease
cauda equina syndrome
type 1 GD


Eltrombopag for Delayed Platelet Recovery and Secondary Thrombocytopenia Following Allogeneic Stem Cell Transplantation in Children.

The delay in platelet recovery after hematopoietic stem cell transplantation (HSCT) is closely related to the overall survival rate of transplanted children. The use of platelet-producing agents such as eltrombopag and romiplostim has made great progress in treating diseases such as immune thrombocytopenia and aplastic anemia. However, the use of such drugs in patients with thrombocytopenia after transplantation, especially in children, is rare. This study aimed to report eltrombopag treatment for 3 children with primary platelet engraftment failure and secondary thrombocytopenia after allogeneic HSCT. Of these patients, 2 had platelets stabilized at ≥50×10/L after eltrombopag treatment and subsequent withdrawal of eltrombopag. All 3 patients showed no clear adverse reactions. The results indicated a wide application prospect of eltrombopag treatment in children with thrombocytopenia after allogeneic HSCT.

The delay in

    platelet recovery
    BIOCHEMICAL

 after

    hematopoietic stem cell transplantation (HSCT)
    MEDICATION

 is closely related to the overall survival rate of transplanted

    children
    AGE

. The use of

    platelet-producing agents such as eltrombopag and romiplostim
    MEDICATION

 has made great progress in treating diseases such as

    immune thrombocytopenia
    DIAGNOSIS

 and

    aplastic anemia
    DIAGNOSIS

. However, the use of such drugs in patients with

    thrombocytopenia
    BIOCHEMICAL

 after

    transplantation
    MEDICATION

, especially in

    children
    AGE

, is rare. This study aimed to report

    eltrombopag treatment
    MEDICATION

 for 3

    children
    AGE

 with

    primary platelet engraftment failure
    SYMPTOMS

 and

    secondary thrombocytopenia
    BIOCHEMICAL

 after

    allogeneic HSCT
    MEDICATION

. Of these patients, 2 had

    platelets stabilized at ≥50×10/L
    BIOCHEMICAL

 after

    eltrombopag treatment and subsequent withdrawal of eltrombopag
    MEDICATION

. All 3 patients showed

    no clear adverse reactions
    NEG_FINDINGS

. The results indicated a wide application prospect of

    eltrombopag treatment
    MEDICATION

 in

    children
    AGE

 with

    thrombocytopenia
    BIOCHEMICAL

 after

    allogeneic HSCT
    MEDICATION

.

platelet recovery
thrombocytopenia
secondary thrombocytopenia
platelets stabilized at ≥50×10/L
thrombocytopenia


A Saudi Infant with Vici Syndrome: Case Report and Literature Review.

Vici syndrome, a rare autosomal recessive disorder, was first described in 1988 by Vici et al. Only 78 cases have been reported to date. The syndrome is characterised by agenesis of the corpus callosum, hypopigmentation, cardiomyopathy, progressive failure to thrive, dysmorphic features, immunodeficiency and cataracts. Mutations in the gene epg5 have been identified as the cause of Vici syndrome.

The parents are a consanguineous Saudi couple with two other children diagnosed with Gaucher disease. The patient was born at term and in the first 5 months had many hospital admissions for a recurrent chest infection. Physical examination, investigations and imaging studies revealed that the patient had agenesis of the corpus callosum, cataracts, psychomotor delay, immunodeficiency and hypopigmentation. The initial echocardiogram was normal. At 7 months, genetic testing confirmed the diagnosis of Vici syndrome with a c.3693G>Ap (Gln1231Gln) mutation in the gene EPG5. The patient developed a chest infection and was admitted to the pediatric intensive care unit. An echocardiogram was repeated and showed significant left ventricular dilation with a Z-score of 3.1, moderate mitral and tricuspid regurgitation, and depressed ventricular function with a fractional shortening of 17% and ejection fraction 37%. The patient's condition deteriorated, and he died aged 8 months.

The symptoms of extensive system involvement in Vici syndrome have been present in the majority of reported cases and should prompt careful evaluation of this syndrome when such symptoms are present in an infant. In confirmed cases, close monitoring of the immune status and cardiac function, the two main causes of death among Vici syndrome patients, is vital to prevent rapid deterioration and improve life expectancy.

    Vici syndrome
    DIAGNOSIS

, a

    rare autosomal recessive disorder
    GENETICS

, was first described in 1988 by Vici et al. Only 78 cases have been reported to date. The syndrome is characterised by

    agenesis of the corpus callosum
    SYMPTOMS

,

    hypopigmentation
    SYMPTOMS

,

    cardiomyopathy
    SYMPTOMS

,

    progressive failure to thrive
    SYMPTOMS

,

    dysmorphic features
    SYMPTOMS

,

    immunodeficiency
    SYMPTOMS

 and

    cataracts
    SYMPTOMS

.

    Mutations in the gene epg5
    GENETICS

 have been identified as the cause of

    Vici syndrome
    DIAGNOSIS

.

    The parents are a consanguineous Saudi
    FAMILY

    couple with two other children diagnosed with Gaucher disease
    FAMILY

. The patient was born at term and in the

    first 5 months
    AGE

 had

    many hospital admissions
    MEDICATION

 for a

    recurrent chest infection
    SYMPTOMS

.

    Physical examination
    PARACLINICAL

,

    investigations
    PARACLINICAL

 and

    imaging studies
    PARACLINICAL

 revealed that the patient had

    agenesis of the corpus callosum
    SYMPTOMS

,

    cataracts
    SYMPTOMS

,

    psychomotor delay
    SYMPTOMS

,

    immunodeficiency
    SYMPTOMS

 and

    hypopigmentation
    SYMPTOMS

. The

    initial echocardiogram was normal
    NEG_FINDINGS

.

    At 7 months
    AGE

,

    genetic testing
    PARACLINICAL

 confirmed the diagnosis of

    Vici syndrome
    DIAGNOSIS

 with a

    c.3693G>Ap (Gln1231Gln) mutation in the gene EPG5
    GENETICS

. The patient developed a

    chest infection
    SYMPTOMS

 and was

    admitted to the pediatric intensive care unit
    MEDICATION

. An

    echocardiogram
    PARACLINICAL

 was repeated and showed

    significant left ventricular dilation with a Z-score of 3.1
    SYMPTOMS

,

    moderate mitral and tricuspid regurgitation
    SYMPTOMS

, and

    depressed ventricular function with a fractional shortening of 17% and ejection fraction 37%
    SYMPTOMS

. The patient's condition deteriorated, and

    he
    GENDER

    died
    SYMPTOMS

    aged 8 months
    AGE

.

The symptoms of

    extensive system involvement
    SYMPTOMS

 in

    Vici syndrome
    DIAGNOSIS

 have been present in the majority of reported cases and should prompt careful evaluation of this syndrome when such symptoms are present in an

    infant
    AGE

. In confirmed cases,

    close monitoring of the immune status and cardiac function
    PARACLINICAL

, the two main causes of

    death
    SYMPTOMS

 among

    Vici syndrome
    DIAGNOSIS

 patients, is vital to prevent

    rapid deterioration
    SYMPTOMS

 and

    improve life expectancy
    SYMPTOMS

.

Vici syndrome
Vici syndrome
Vici syndrome
Vici syndrome
Vici syndrome


A novel mutation causing type 1 Gaucher disease found in a Japanese patient with gastric cancer: A case report.

Gaucher disease (GD) is an autosomal recessive disorder that leads to multiorgan complications caused by β-glucocerebrosidase deficiency due to mutations in the β-glucocerebrosidase-encoding gene (GBA). GD morbidity in Japan is quite rare and clinical phenotype and gene mutation patterns of patients with GD in Japan and Western countries differ considerably. Of Japanese patients with GD, 57% develop types 2 or 3 GD with neurologic manifestations and younger onset, whereas only 6% of patients with GD develop those manifestations in Western countries. Thus, it is relatively difficult to find and diagnose GD in Japan.

A 69-year-old Japanese female with mild anemia and thrombocytopenia but without neurologic symptoms was initially referred for gastric cancer. Preoperative F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed accumulation in the bone marrow and paraabdominal lymph nodes. Following bone marrow aspiration found, abnormal foamy macrophages in the bone marrow and electron microscopy revealed that the macrophages were filled with tubular-form structures. Adding to these signs suggestive of a lysosomal disease, serum β-glucocerebrosidase activity test found decreased. Sequencing of the patient's GBA gene revealed a RecNciI recombinant mutation and the novel mutation K157R (c.587A>G).

On the basis of these findings and clinical manifestations, the final diagnosis of type 1 GD was made.

Enzyme replacement therapy (ERT) with velaglucerase α was started after the diagnosis of type 1 GD.

The patient's β-glucocerebrosidase activity as well as hemoglobin and platelet levels were restored by ERT without any side effects. Bone marrow aspirations 10 months after the start of the treatment with velaglucerase α showed reduction of Gaucher cells in bone marrow to 2% from 4% of total cellularity.

This is the first report of F-FDG PET/CT application providing a clue for GD diagnosis. A novel mutation in GBA is described, which implies a potential pool of patients with GD with this mutation in Japan.

    Gaucher disease (GD)
    DIAGNOSIS

 is an

    autosomal recessive disorder
    GENETICS

 that leads to

    multiorgan complications
    SYMPTOMS

 caused by

    β-glucocerebrosidase deficiency
    BIOCHEMICAL

 due to

    mutations in the β-glucocerebrosidase-encoding gene (GBA)
    GENETICS

.

    GD
    DIAGNOSIS

 morbidity in

    Japan
    ETHNICITY

 is quite rare and clinical phenotype and

    gene mutation patterns
    GENETICS

 of patients with

    GD
    DIAGNOSIS

 in

    Japan
    ETHNICITY

 and Western countries differ considerably. Of

    Japanese
    ETHNICITY

 patients with

    GD
    DIAGNOSIS

, 57% develop

    types 2 or 3 GD
    DIAGNOSIS

 with

    neurologic manifestations
    SYMPTOMS

 and

    younger onset
    AGE

, whereas only 6% of patients with

    GD
    DIAGNOSIS

 develop those manifestations in Western countries. Thus, it is relatively difficult to find and diagnose

    GD
    DIAGNOSIS

 in

    Japan
    ETHNICITY

.

A

    69-year-old
    AGE

    Japanese
    ETHNICITY

    female
    GENDER

 with

    mild anemia
    BIOCHEMICAL

 and

    thrombocytopenia
    BIOCHEMICAL

 but

    without neurologic symptoms
    NEG_FINDINGS

 was initially referred for

    gastric cancer
    DIAGNOSIS

.

    Preoperative F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT)
    PARACLINICAL

 showed

    accumulation in the bone marrow and paraabdominal lymph nodes
    MICROSCOPIC

. Following

    bone marrow aspiration
    PARACLINICAL

 found,

    abnormal foamy macrophages in the bone marrow
    MICROSCOPIC

 and

    electron microscopy
    PARACLINICAL

 revealed that

    the macrophages were filled with tubular-form structures
    MICROSCOPIC

. Adding to these signs suggestive of a

    lysosomal disease
    DIAGNOSIS

,

    serum β-glucocerebrosidase activity test found decreased
    BIOCHEMICAL

.

    Sequencing of the patient's GBA gene
    PARACLINICAL

 revealed a RecNciI recombinant mutation and the novel mutation K157R (c.587A>G).

On the basis of these findings and clinical manifestations, the final diagnosis of

    type 1 GD
    DIAGNOSIS

 was made.

    Enzyme replacement therapy (ERT) with velaglucerase α
    MEDICATION

 was started after the diagnosis of

    type 1 GD
    DIAGNOSIS

.

The patient's

    β-glucocerebrosidase activity as well as hemoglobin and platelet levels were restored
    BIOCHEMICAL

 by

    ERT
    MEDICATION

    without any side effects
    NEG_FINDINGS

.

    Bone marrow aspirations
    PARACLINICAL

 10 months after the start of the

    treatment with velaglucerase α
    MEDICATION

 showed

    reduction of Gaucher cells in bone marrow to 2% from 4% of total cellularity
    MICROSCOPIC

.

This is the first report of

    F-FDG PET/CT
    PARACLINICAL

 application providing a clue for

    GD
    DIAGNOSIS

 diagnosis. A

    novel mutation in GBA
    GENETICS

 is described, which implies a potential pool of patients with

    GD
    DIAGNOSIS

 with this mutation in

    Japan
    ETHNICITY

.

Gaucher disease (GD)
GD
GD
GD
types 2 or 3 GD
GD
GD
gastric cancer
lysosomal disease
type 1 GD
type 1 GD
GD
GD

multiorgan complications
neurologic manifestations

Japan Japan Japanese Japan Japanese Japan

without neurologic symptoms
without any side effects


Gaucher Disease and Myelofibrosis: A Combined Disease or a Misdiagnosis?

Gaucher disease (GD) and primary myelofibrosis (PMF) share similar clinical and laboratory features, such as cytopenia, hepatosplenomegaly, and marrow fibrosis, often resulting in a misdiagnosis.

We report here the case of a young woman with hepatosplenomegaly, leukopenia, and thrombocytopenia. Based on bone marrow (BM) findings and on liver biopsy showing extramedullary hematopoiesis, an initial diagnosis of PMF was formulated. The patient refused stem cell transplantation from an HLA-identical sibling. Low-dose melphalan was given, without any improvement. Two years later, a BM evaluation showed Gaucher cells. Low glucocerebrosidase and high chitotriosidase levels were indicative for GD. Molecular analysis revealed N370S/complex I mutations. Enzyme replacement therapy with imiglucerase was commenced, resulting in clinical and hematological improvements. Due to an unexpected and persistent organomegaly, PMF combined with GD were suspected. JAK2V617F, JAK2 exon 12, MPL, calreticulin, and exon 9 mutations were negative, and BM examination showed no marrow fibrosis. PMF was excluded. Twenty years after starting treatment, the peripheral cell count and liver size were normal, whereas splenomegaly persisted.

In order to avoid a misdiagnosis, a diagnostic algorithm for patients with hepatosplenomegaly combined with cytopenia is suggested.

    Gaucher disease (GD)
    DIAGNOSIS

 and

    primary myelofibrosis (PMF)
    DIAGNOSIS

 share similar clinical and laboratory features, such as

    cytopenia
    BIOCHEMICAL

,

    hepatosplenomegaly
    SYMPTOMS

, and

    marrow fibrosis
    SYMPTOMS

, often resulting in a

    misdiagnosis
    NEG_FINDINGS

.

We report here the case of a

    young
    AGE

    woman
    GENDER

 with

    hepatosplenomegaly
    SYMPTOMS

,

    leukopenia
    BIOCHEMICAL

, and

    thrombocytopenia
    BIOCHEMICAL

. Based on

    bone marrow (BM) findings
    PARACLINICAL

 and on

    liver biopsy
    PARACLINICAL

 showing

    extramedullary hematopoiesis
    MICROSCOPIC

, an initial diagnosis of

    PMF
    DIAGNOSIS

 was formulated. The patient

    refused stem cell transplantation from an HLA-identical sibling
    NEG_FINDINGS

.

    Low-dose melphalan was given, without any improvement
    NEG_FINDINGS

. Two years later, a

    BM evaluation
    PARACLINICAL

 showed

    Gaucher cells
    MICROSCOPIC

.

    Low glucocerebrosidase
    BIOCHEMICAL

 and

    high chitotriosidase levels
    BIOCHEMICAL

 were indicative for

    GD
    DIAGNOSIS

.

    Molecular analysis
    PARACLINICAL

 revealed

    N370S/complex I mutations
    GENETICS

.

    Enzyme replacement therapy with imiglucerase
    MEDICATION

 was commenced, resulting in

    clinical and hematological improvements
    SYMPTOMS

. Due to an unexpected and

    persistent organomegaly
    SYMPTOMS

,

    PMF combined with GD
    DIAGNOSIS

 were suspected.

    JAK2V617F, JAK2 exon 12, MPL, calreticulin, and exon 9 mutations were negative
    NEG_FINDINGS

, and

    BM examination
    PARACLINICAL

 showed

    no marrow fibrosis
    NEG_FINDINGS

.

    PMF was excluded
    NEG_FINDINGS

. Twenty years after starting treatment,

    the peripheral cell count and liver size were normal
    NEG_FINDINGS

, whereas

    splenomegaly persisted
    SYMPTOMS

.

In order to avoid a misdiagnosis, a diagnostic algorithm for patients with

    hepatosplenomegaly
    SYMPTOMS

 combined with

    cytopenia
    BIOCHEMICAL

 is suggested.

Gaucher disease (GD)
primary myelofibrosis (PMF)
PMF
GD
PMF combined with GD

cytopenia
leukopenia
thrombocytopenia
Low glucocerebrosidase
high chitotriosidase levels
cytopenia

hepatosplenomegaly
marrow fibrosis
hepatosplenomegaly
clinical and hematological improvements
persistent organomegaly
splenomegaly persisted
hepatosplenomegaly


Perinatal Lethal Gaucher Disease due to RecNcil Recombinant Mutation in the GBA Gene Presenting with Hydrops Fetalis and Severe Congenital Anemia.

A 35-year-old woman presented at 27-week gestation with hypertension and pedal edema. Antenatal scan showed hydrops fetalis and growth restriction. Cordocentesis showed severe fetal anemia. This was treated with multiple in utero blood transfusions with no clinically significant improvement and intrauterine death occurred at 28 weeks. Perinatal autopsy confirmed severe hydrops with hepatosplenomegaly and visceral effusions. Microscopic examination of the reticuloendothelial organs showed widespread infiltration by large mono- and multinucleate histiocytic cells with fibrillary appearance ("Gaucher cells"). DNA extracted from fetal tissue was submitted for analysis by next generation sequencing which revealed homozygosity for the RecNcil mutation in the GBA gene. Both parents were found to be heterozygous for the variant. The case report highlights a severe form of Gaucher disease with histopathological and molecular confirmation that presents with hydrops fetalis and severe refractory anemia. It also emphasizes the importance of perinatal autopsy coupled with exome sequencing in confirming syndromic diagnosis in the modern area.

A

    35-year-old
    AGE

    woman
    GENDER

 presented at

    27-week gestation
    SYMPTOMS

 with

    hypertension
    SYMPTOMS

 and

    pedal edema
    SYMPTOMS

.

    Antenatal scan
    PARACLINICAL

 showed

    hydrops fetalis
    DIAGNOSIS

 and

    growth restriction
    SYMPTOMS

.

    Cordocentesis
    PARACLINICAL

 showed

    severe fetal anemia
    BIOCHEMICAL

. This was

    treated with multiple in utero blood transfusions with no clinically significant improvement
    NEG_FINDINGS

 and

    intrauterine death
    SYMPTOMS

 occurred

    at 28 weeks
    AGE

.

    Perinatal autopsy
    PARACLINICAL

 confirmed

    severe hydrops
    DIAGNOSIS

 with

    hepatosplenomegaly
    SYMPTOMS

 and

    visceral effusions
    SYMPTOMS

.

    Microscopic examination of the reticuloendothelial organs
    PARACLINICAL

 showed

    widespread infiltration by large mono- and multinucleate histiocytic cells with fibrillary appearance ("Gaucher cells")
    MICROSCOPIC

.

    DNA extracted from fetal tissue was submitted for analysis by next generation sequencing
    PARACLINICAL

 which revealed

    homozygosity for the RecNcil mutation in the GBA gene
    GENETICS

.

    Both parents were found to be heterozygous for the variant
    FAMILY

. The case report highlights a

    severe form of Gaucher disease
    DIAGNOSIS

 with

    histopathological and molecular confirmation
    PARACLINICAL

 that presents with

    hydrops fetalis
    DIAGNOSIS

 and

    severe refractory anemia
    BIOCHEMICAL

. It also emphasizes the importance of

    perinatal autopsy
    PARACLINICAL

 coupled with

    exome sequencing
    PARACLINICAL

 in confirming syndromic diagnosis in the modern area.

27-week gestation
hypertension
pedal edema
growth restriction
intrauterine death
hepatosplenomegaly
visceral effusions

hydrops fetalis
severe hydrops
severe form of Gaucher disease
hydrops fetalis

severe fetal anemia
severe refractory anemia


The motor and cognitive features of Parkinson's disease in patients with concurrent Gaucher disease over 2 years: a case series.

We report the cognitive features and progression of Parkinson's disease (PD) in five patients with concurrent Gaucher disease. The patients presented at an earlier age than patients with sporadic PD, as previously noted by others; but in contrast to many previous reports, our patients followed a variable clinical course. While two patients developed early cognitive deficits and dementia, three others remained cognitively intact over the follow-up period. Thus, in this small case series, PD in the context of GD more closely resembles idiopathic PD in terms of its clinical heterogeneity in contrast to PD associated with GBA heterozygote mutations.

We report the cognitive features and progression of

    Parkinson's disease (PD)
    DIAGNOSIS

 in five patients with

    concurrent Gaucher disease
    DIAGNOSIS

. The patients presented at an

    earlier age
    AGE

 than patients with

    sporadic PD
    DIAGNOSIS

, as previously noted by others; but in contrast to many previous reports, our patients followed a variable clinical course. While two patients developed

    early cognitive deficits
    SYMPTOMS

 and

    dementia
    SYMPTOMS

, three others

    remained cognitively intact over the follow-up period
    NEG_FINDINGS

. Thus, in this small case series,

    PD
    DIAGNOSIS

 in the context of

    GD
    DIAGNOSIS

 more closely resembles

    idiopathic PD
    DIAGNOSIS

 in terms of its clinical heterogeneity in contrast to

    PD
    DIAGNOSIS

 associated with

    GBA heterozygote mutations
    GENETICS

.

Parkinson's disease (PD)
concurrent Gaucher disease
sporadic PD
PD
GD
idiopathic PD
PD


Gaucher disease and chronic myeloid leukemia: first reported patient receiving enzyme replacement and tyrosine kinase inhibitor therapies simultaneously.

Report a female diagnosed as type 1 Gaucher disease after a femoral pathologic fracture when she was 55 years old. Enzyme replacement therapy was started, and she achieved therapeutic goals. In 2015, a Ph' CML with numerous pseudo-Gaucher cells in bone marrow appears. BCR/ABL was not present at GD diagnosis.

Report a

    female
    GENDER

 diagnosed as

    type 1 Gaucher disease
    DIAGNOSIS

 after a

    femoral pathologic fracture
    SYMPTOMS

 when

    she
    GENDER

 was

    55 years old
    AGE

.

    Enzyme replacement therapy
    MEDICATION

 was started, and

    she
    GENDER

 achieved

    therapeutic goals
    SYMPTOMS

. In 2015, a

    Ph' CML
    MICROSCOPIC

 with

    numerous pseudo-Gaucher cells in bone marrow appears
    MICROSCOPIC

.

    BCR/ABL was not present at GD diagnosis
    NEG_FINDINGS

.

femoral pathologic fracture
therapeutic goals


Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey.

Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (<1%). Three of the patients had novel mutations, one of them was a collodion baby and the other one was mistyped as type III due to its atypical presentation at the beginning and he was treated with ERT for 8 months. In this report, we present our type II Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type.

    Gaucher disease
    DIAGNOSIS

 is the most common

    lysosomal storage disorder
    DIAGNOSIS

 due to

    glucosylceramidase enzyme deficiency
    BIOCHEMICAL

. There are three subtypes of the disease.

    Neurological involvement
    SYMPTOMS

 accompanies

    visceral and haematological findings
    SYMPTOMS

 only in

    type II
    DIAGNOSIS

 and

    type III Gaucher
    DIAGNOSIS

 patients.

    Type II
    DIAGNOSIS

 is the

    acute progressive neuronopathic form
    DIAGNOSIS

 which is the most severe and rare subtype. Clinical findings are recognized

    prenatally or in the first months of life
    AGE

 and followed by

    death
    SYMPTOMS

    within the first two years of age
    AGE

. Among our 81

    Gaucher
    DIAGNOSIS

 patients, we identified 4 (4,9%)

    type II
    DIAGNOSIS

 patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (<1%). Three of the patients had

    novel mutations
    GENETICS

, one of them was a

    collodion baby
    DIAGNOSIS

 and the other one was

    mistyped as type III
    NEG_FINDINGS

 due to its atypical presentation at the beginning and

    he
    GENDER

 was

    treated with ERT for 8 months
    MEDICATION

. In this report, we present our

    type II Gaucher
    DIAGNOSIS

 patients with

    three novel mutations
    GENETICS

 and one

    perinatal lethal form
    DIAGNOSIS

 with

    generalized ichthyosis
    SYMPTOMS

 which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type.

Gaucher disease
lysosomal storage disorder
type II
type III Gaucher
Type II
acute progressive neuronopathic form
Gaucher
type II
collodion baby
type II Gaucher
perinatal lethal form

Neurological involvement
visceral and haematological findings
death
generalized ichthyosis


Thromboelastography Before Epidural Placement in a Thrombocytopenic Parturient With Gaucher Disease Treated With Imiglucerase: A Case Report.

Gaucher disease is a common inborn error of metabolism leading to widespread chronic inflammation and often thrombocytopenia. Here we discuss assessment of coagulation in a parturient with Gaucher disease treated with imiglucerase, who presented with thrombocytopenia and requested epidural analgesia for planned vaginal delivery. We used thromboelastography to determine the safety of placing an epidural catheter and to plan for potential peripartum bleeding. The patient had a normal coagulation profile by thromboelastography and had uncomplicated epidural analgesia for a successful spontaneous vaginal delivery.

    Gaucher disease
    DIAGNOSIS

 is a common

    inborn error of metabolism
    GENETICS

 leading to

    widespread chronic inflammation
    MICROSCOPIC

 and often

    thrombocytopenia
    BIOCHEMICAL

. Here we discuss

    assessment of coagulation
    PARACLINICAL

 in a

    parturient
    AGE

 with

    Gaucher disease
    DIAGNOSIS

 treated with

    imiglucerase
    MEDICATION

, who presented with

    thrombocytopenia
    BIOCHEMICAL

 and requested

    epidural analgesia
    MEDICATION

 for

    planned vaginal delivery
    MEDICATION

. We used

    thromboelastography
    PARACLINICAL

 to determine the safety of

    placing an epidural catheter
    MEDICATION

 and to plan for potential

    peripartum bleeding
    SYMPTOMS

. The patient had a

    normal coagulation profile by thromboelastography
    NEG_FINDINGS

 and had

    uncomplicated epidural analgesia
    MEDICATION

 for a

    successful spontaneous vaginal delivery
    MEDICATION

.

imiglucerase
epidural analgesia
planned vaginal delivery
placing an epidural catheter
uncomplicated epidural analgesia
successful spontaneous vaginal delivery


[Type 3 Gaucher disease, also an adult disease?]

Gaucher disease is a genetic lysosomal storage disorder due to a glucocerebrosidase deficiency. Type 3, including neurological impairment, may have a specific phenotype in the context of the D409H mutation.

We report the case of a 22-year-old woman who presented with Gaucher disease. Enzyme replacement therapy by imiglucerase was followed by rapid clinical and biological improvement. However, communication difficulties, which were initially attributed to the language barrier, revealed neurological impairment. After complementary assessment, the diagnosis of type 3 Gaucher disease was suspected. Gene analysis of the glucocerebrosidase showed a homozygous D409H mutation.

This mutation results in calcified heart valves, corneal opacities, alteration of oculomotricity and hydrocephalus. The mild manifestation at onset and the late neurological involvement in the medical history make the diagnosis more difficult. This particular clinical phenotype deserves to be known in adult medicine departments.

    Gaucher disease
    DIAGNOSIS

 is a

    genetic lysosomal storage disorder
    DIAGNOSIS

 due to a

    glucocerebrosidase deficiency
    BIOCHEMICAL

.

    Type 3
    DIAGNOSIS

, including

    neurological impairment
    SYMPTOMS

, may have a specific phenotype in the context of the

    D409H mutation
    GENETICS

.

We report the case of a

    22-year-old
    AGE

    woman
    GENDER

 who presented with

    Gaucher disease
    DIAGNOSIS

.

    Enzyme replacement therapy by imiglucerase
    MEDICATION

 was followed by

    rapid clinical and biological improvement
    SYMPTOMS

. However,

    communication difficulties, which were initially attributed to the language barrier
    NEG_FINDINGS

, revealed

    neurological impairment
    SYMPTOMS

. After complementary assessment, the diagnosis of

    type 3 Gaucher disease
    DIAGNOSIS

 was suspected.

    Gene analysis of the glucocerebrosidase
    PARACLINICAL

 showed a

    homozygous D409H mutation
    GENETICS

.

This mutation results in

    calcified heart valves
    SYMPTOMS

,

    corneal opacities
    SYMPTOMS

,

    alteration of oculomotricity
    SYMPTOMS

 and

    hydrocephalus
    SYMPTOMS

. The

    mild manifestation at onset
    SYMPTOMS

 and the

    late neurological involvement
    SYMPTOMS

 in the medical history make the diagnosis more difficult. This particular clinical phenotype deserves to be known in adult medicine departments.

Gaucher disease
genetic lysosomal storage disorder
Type 3
Gaucher disease
type 3 Gaucher disease

D409H mutation
homozygous D409H mutation


High-risk screening for Gaucher disease in patients with neurological symptoms.

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by the deficiency of glucocerebrosidase enzyme activity. Clinical phenotypes of GD are categorized into three groups: (i) non-neuronopathic GD (type 1), (ii) acute neuronopathic GD (type 2) and (iii) subacute neuronopathic GD (type 3). The high-risk screening of neuronopathic GD has been performed using an enzymatic assay on the dried blood spot (DBS) samples. We enrolled a total of 102 individuals (47 females, 55 males; 0-57 years old; median age 10.5 years) with various neurological symptoms. We detected two patients with very low enzyme activity and they were diagnosed with the disease by using glucocerebrosidase gene analysis. Patient 1 was found to be compound heterozygous for the p.R159W/p.R170C locus and patient 2 was found to harbor two mutations at the IVS7+1G>T (c.999+1G>T) and p.L483P sites. This simple screening protocol using DBS samples is useful for early diagnosis of GD in high-risk and underdiagnosed patients suffering from various neurological symptoms.

    Gaucher disease (GD)
    DIAGNOSIS

 is an

    autosomal recessive
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 caused by the

    deficiency of glucocerebrosidase enzyme activity
    BIOCHEMICAL

. Clinical phenotypes of

    GD
    DIAGNOSIS

 are categorized into three groups: (i)

    non-neuronopathic GD (type 1)
    DIAGNOSIS

, (ii)

    acute neuronopathic GD (type 2)
    DIAGNOSIS

 and (iii)

    subacute neuronopathic GD (type 3)
    DIAGNOSIS

. The high-risk screening of

    neuronopathic GD
    DIAGNOSIS

 has been performed using an

    enzymatic assay on the dried blood spot (DBS) samples
    PARACLINICAL

. We enrolled a total of 102 individuals (47

    females
    GENDER

, 55

    males
    GENDER

;

    0-57 years old
    AGE

;

    median age 10.5 years
    AGE

) with

    various neurological symptoms
    SYMPTOMS

. We detected two patients with

    very low enzyme activity
    BIOCHEMICAL

 and they were diagnosed with the disease by using

    glucocerebrosidase gene analysis
    PARACLINICAL

. Patient 1 was found to be

    compound heterozygous for the p.R159W/p.R170C locus
    GENETICS

 and patient 2 was found to harbor

    two mutations at the IVS7+1G>T (c.999+1G>T) and p.L483P sites
    GENETICS

. This simple screening protocol using

    DBS samples
    PARACLINICAL

 is useful for early diagnosis of

    GD
    DIAGNOSIS

 in high-risk and underdiagnosed patients suffering from

    various neurological symptoms
    SYMPTOMS

.

Gaucher disease (GD)
lysosomal storage disorder
GD
non-neuronopathic GD (type 1)
acute neuronopathic GD (type 2)
subacute neuronopathic GD (type 3)
neuronopathic GD
GD

various neurological symptoms
various neurological symptoms


Type I Gaucher disease with bullous pemphigoid and Parkinson disease: A case report.

Gaucher disease (GD) is a rare genetic lysosomal storage disorder inherited in an autosomal recessive pattern. GD is due to the deficiency of a lysosomal enzyme, acid beta-glucosidase (or glucocerebrosidase). Type 1 Gaucher disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen, and liver as well as bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts, and avascular necrosis leading to degenerative arthropathy). The diagnosis is usually made in first decades but is sometimes delayed. Parkinson disease, neoplasia, and immune system abnormalities may be associated with GD1.

A patient known for hepatosplenomegaly with hyperferritinemia, anemia, and thrombocytopenia was admitted for Lewy body dementia and bullous pemphigoid.

Type 1 Gaucher disease.

No specific treatment started.

patient died ten months later due to pneumonia.

To the best of our knowledge, this is the first case of the association between GD1, bullous pemphigoid, and Lewy body dementia. We discuss the central role of alpha-synuclein in these pathologies.

    Gaucher disease (GD)
    DIAGNOSIS

 is a

    rare genetic lysosomal storage disorder
    GENETICS

    inherited in an autosomal recessive pattern
    GENETICS

.

    GD
    DIAGNOSIS

 is due to the

    deficiency of a lysosomal enzyme, acid beta-glucosidase (or glucocerebrosidase)
    BIOCHEMICAL

.

    Type 1 Gaucher disease (GD1)
    DIAGNOSIS

 is characterized by

    thrombocytopenia
    BIOCHEMICAL

,

    anemia
    BIOCHEMICAL

, an

    enlarged spleen, and liver
    SYMPTOMS

 as well as

    bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts, and avascular necrosis leading to degenerative arthropathy)
    SYMPTOMS

. The diagnosis is usually made

    in first decades
    AGE

 but is sometimes delayed.

    Parkinson disease
    DIAGNOSIS

,

    neoplasia
    SYMPTOMS

, and

    immune system abnormalities
    SYMPTOMS

 may be associated with

    GD1
    DIAGNOSIS

.

A patient known for

    hepatosplenomegaly
    SYMPTOMS

 with

    hyperferritinemia
    BIOCHEMICAL

,

    anemia
    BIOCHEMICAL

, and

    thrombocytopenia
    BIOCHEMICAL

 was admitted for

    Lewy body dementia
    DIAGNOSIS

 and

    bullous pemphigoid
    DIAGNOSIS

.

    Type 1 Gaucher disease
    DIAGNOSIS

.

    No specific treatment started
    NEG_FINDINGS

.

patient

    died
    SYMPTOMS

 ten months later due to

    pneumonia
    DIAGNOSIS

.

To the best of our knowledge, this is the first case of the

    association between GD1, bullous pemphigoid, and Lewy body dementia
    DIAGNOSIS

. We discuss the central role of

    alpha-synuclein
    BIOCHEMICAL

 in these pathologies.


EVALUATION OF EFFICIENCY OF IMIGLUCERASE (CEREZYME) IN THE TREATMENT OF GAUCHER DISEASE (CASE REPORTS AND REVIEW OF THE LITERATURE).

The data on occurrence and pathogenetic mechanisms of glucosylceramide lipidosis (Gaucher disease), which is based on the hereditary deficiency of glucocerebrosidase activity -the enzyme involved in the processing of cellular metabolism products, is presented. Clinical and morphological manifestations of the disease, therapeutic tactics and prognosis are defined. A typical clinical case of Gaucher disease type 1 in two adult patients was analyzed. It is shown that timely diagnosis of Gaucher disease allows the prescription of adequate treatment by means of enzyme replacement therapy with cerezyme drug. That is why the correct and timely diagnosis of the disease can prolongate patient's life for many years. In this case, the patient should be under the care of doctors (pediatricians, general physicians, hematologists). Continued treatment of Gaucher disease with cerezyme stabilizes the pathological process completely, decreases significant changes in bones and parenchymal organs, improving patients' lives considerably. For that reason, the sooner the adequate therapy is started, the more effective the results will be.

The data on occurrence and pathogenetic mechanisms of

    glucosylceramide lipidosis (Gaucher disease)
    DIAGNOSIS

, which is based on the

    hereditary
    GENETICS

    deficiency of glucocerebrosidase activity -the enzyme involved in the processing of cellular metabolism products
    BIOCHEMICAL

, is presented. Clinical and morphological manifestations of the disease, therapeutic tactics and prognosis are defined. A typical clinical case of

    Gaucher disease type 1
    DIAGNOSIS

 in two

    adult
    AGE

 patients was analyzed. It is shown that timely diagnosis of

    Gaucher disease
    DIAGNOSIS

 allows the prescription of adequate treatment by means of

    enzyme replacement therapy with cerezyme drug
    MEDICATION

. That is why the correct and timely diagnosis of the disease can prolongate patient's life for many years. In this case, the patient should be under the care of doctors (

    pediatricians
    PARACLINICAL

,

    general physicians
    PARACLINICAL

,

    hematologists
    PARACLINICAL

).

    Continued treatment
    MEDICATION

 of

    Gaucher disease
    DIAGNOSIS

    with cerezyme
    MEDICATION

    stabilizes the pathological process completely
    SYMPTOMS

,

    decreases significant changes in bones and parenchymal organs
    SYMPTOMS

, improving patients' lives considerably. For that reason, the sooner the adequate therapy is started, the more effective the results will be.


Laparoscopic fenestration for a huge symptomatic splenic cyst in a patient with Gaucher's disease.

A 34-year-old woman visited our hospital for treatment of a huge splenic cyst with epigastric pain. She had been diagnosed with Gaucher's disease (Type 1) at 3 years of age and had been receiving enzyme replacement therapy (ERT) from 15 years of age. Abdominal MRI showed a low-intensity area, 30 cm in diameter, with a well-defined border on T1-weighted images. The patient underwent laparoscopic fenestration of the huge splenic cyst for relief of worsening epigastric pain caused by the cyst. The cyst contained 2,500 ml of brownish-red fluid. The patient recovered satisfactorily and was discharged on postoperative day 11. Gaucher's disease is an extremely rare metabolic disease; only about 6,000 patients are registered in the International Collaborative Gaucher Group Gaucher Registry. An extremely rare case of a huge symptomatic splenic cyst treated by laparoscopic fenestration in a patient with Gaucher's disease is described.

A

    34-year-old
    AGE

    woman
    GENDER

 visited our hospital for treatment of a

    huge splenic cyst
    SYMPTOMS

 with

    epigastric pain
    SYMPTOMS

.

    She
    GENDER

 had been diagnosed with

    Gaucher's disease (Type 1)
    DIAGNOSIS

 at

    3 years of age
    AGE

 and had been

    receiving enzyme replacement therapy (ERT)
    MEDICATION

    from 15 years of age
    AGE

.

    Abdominal MRI
    PARACLINICAL

 showed a

    low-intensity area, 30 cm in diameter, with a well-defined border on T1-weighted images
    SYMPTOMS

. The patient underwent

    laparoscopic fenestration of the huge splenic cyst
    MEDICATION

 for relief of

    worsening epigastric pain caused by the cyst
    SYMPTOMS

. The

    cyst contained 2,500 ml of brownish-red fluid
    SYMPTOMS

. The patient recovered satisfactorily and was discharged on postoperative day 11.

    Gaucher's disease
    DIAGNOSIS

 is an

    extremely rare metabolic disease
    DIAGNOSIS

; only about 6,000 patients are registered in the International Collaborative Gaucher Group Gaucher Registry. An extremely rare case of a

    huge symptomatic splenic cyst
    SYMPTOMS

 treated by

    laparoscopic fenestration
    MEDICATION

 in a patient with

    Gaucher's disease
    DIAGNOSIS

 is described.

Gaucher's disease (Type 1)
Gaucher's disease
extremely rare metabolic disease
Gaucher's disease


Gaucher's disease in a patient presenting with hip and abdominal pain.

Gaucher's disease is characterized by glucocerebroside accumulation in the cells of the reticuloendothelial system. There are three subtypes. The most common is type 1, known as the non-neuropathic form. Pancytopenia, hepatosplenomegaly and bone lesions occur as a result of glucocerebroside accumulation in the liver, lung, spleen and bone marrow in these patients. Findings associated with liver, spleen or bone involvement may be seen at radiological analysis. Improvement in extraskeletal system findings is seen with enzyme replacement therapy. Support therapy is added in patients developing infection, anemia or pain. We describe a case of hepatosplenomegaly, splenic infarction, splenic nodules and femur fracture determined at radiological imaging in a patient under monitoring due to Gaucher's disease.

    Gaucher's disease
    DIAGNOSIS

 is characterized by

    glucocerebroside accumulation in the cells of the reticuloendothelial system
    MICROSCOPIC

. There are three subtypes. The most common is

    type 1
    DIAGNOSIS

, known as the

    non-neuropathic form
    DIAGNOSIS

.

    Pancytopenia
    BIOCHEMICAL

,

    hepatosplenomegaly
    SYMPTOMS

 and

    bone lesions
    SYMPTOMS

 occur as a result of

    glucocerebroside accumulation in the liver, lung, spleen and bone marrow
    MICROSCOPIC

 in these patients.

    Findings associated with liver, spleen or bone involvement
    SYMPTOMS

 may be seen at

    radiological analysis
    PARACLINICAL

.

    Improvement in extraskeletal system findings
    SYMPTOMS

 is seen with

    enzyme replacement therapy
    MEDICATION

.

    Support therapy
    MEDICATION

 is added in patients developing

    infection
    SYMPTOMS

,

    anemia
    BIOCHEMICAL

 or

    pain
    SYMPTOMS

. We describe a case of

    hepatosplenomegaly
    SYMPTOMS

,

    splenic infarction
    SYMPTOMS

,

    splenic nodules
    SYMPTOMS

 and

    femur fracture
    SYMPTOMS

 determined at

    radiological imaging
    PARACLINICAL

 in a patient under monitoring due to

    Gaucher's disease
    DIAGNOSIS

.

Gaucher's disease
type 1
non-neuropathic form
Gaucher's disease

enzyme replacement therapy
Support therapy


Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods.

We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy.

While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy and enzyme replacement therapy, the current case reports demonstrate that judicious use of combination therapy may be of benefit in some cases.

    Intravenous enzyme replacement therapy
    MEDICATION

 is a first-line therapy for

    Gaucher disease type 1
    DIAGNOSIS

, and

    substrate reduction therapy
    MEDICATION

 represents an

    oral treatment alternative
    MEDICATION

. Both

    enzyme replacement therapy and substrate reduction therapy
    MEDICATION

 are generally used as

    monotherapies
    MEDICATION

 in

    Gaucher disease
    DIAGNOSIS

. However, one randomized study and several case reports have described

    combination therapy over short time periods
    MEDICATION

.

We report two

    female
    GENDER

    Gaucher disease type 1
    DIAGNOSIS

 patients of mainly

    Anglo-Saxon descent
    ETHNICITY

, where

    combined enzyme replacement therapy and miglustat substrate reduction therapy
    MEDICATION

 were administered to overcome

    refractory clinical symptoms
    SYMPTOMS

. The first patient was diagnosed at

    age 17
    AGE

 and developed

    Gaucher disease-related bone manifestations
    SYMPTOMS

 that

    worsened despite starting imiglucerase enzyme replacement therapy
    NEG_FINDINGS

. After

    switching to miglustat substrate reduction therapy
    MEDICATION

,

    her
    GENDER

    bone symptoms improved
    SYMPTOMS

, but

    she
    GENDER

 developed

    tremors
    SYMPTOMS

 and eventually

    switched back to enzyme replacement therapy
    MEDICATION

.

    Miglustat
    MEDICATION

 was later recommenced

    in combination with ongoing enzyme replacement therapy
    MEDICATION

 due to continued

    bone pain
    SYMPTOMS

, and

    her
    GENDER

    bone symptoms improved
    SYMPTOMS

 along with

    maintained visceral manifestations
    SYMPTOMS

.

    Enzyme replacement therapy was subsequently tapered off
    MEDICATION

 and the patient has since been successfully

    maintained on miglustat
    MEDICATION

. The second patient was diagnosed

    aged 3
    AGE

, and

    commenced imiglucerase enzyme replacement therapy
    MEDICATION

    aged 15
    AGE

.

    After 9 years on enzyme replacement therapy
    MEDICATION

    she
    GENDER

    switched to miglustat substrate reduction therapy
    MEDICATION

 and

    her
    GENDER

    core symptoms were maintained/stable for 3 years
    SYMPTOMS

.

    Imiglucerase enzyme replacement therapy was later added as a boost to therapy
    MEDICATION

 and

    her
    GENDER

    symptoms were subsequently maintained over a 2.3-year period
    SYMPTOMS

. However,

    miglustat was discontinued
    MEDICATION

 due to

    her
    GENDER

 relocation, necessitating an

    increase in enzyme replacement therapy dose
    MEDICATION

. Overall, both patients benefited from

    combination therapy
    MEDICATION

.

While the majority of

    Gaucher disease type 1
    DIAGNOSIS

 patients will not need

    treatment with both substrate reduction therapy and enzyme replacement therapy
    MEDICATION

, the current case reports demonstrate that judicious use of

    combination therapy
    MEDICATION

 may be of benefit in some cases.

Gaucher disease type 1
Gaucher disease
Gaucher disease type 1
Gaucher disease type 1


Actual reason for bone fractures in the case of a patient followed-up with the osteogenesis imperfecta: Gaucher's Disease.

Gaucher's disease (GD) is a rare disease characterized by a β-glucocerebroside accumulation in the reticulo-endothelial system. Patients may refer to the clinic with complaints of bone pain, hepatosplenomegaly, anemia, thrombocytopenia, growth retardation, interstitial pulmonary disease, pulmonary hypertension, and skeletal disorders. Skeletal system involvement is observed commonly in Gaucher patients and a significant cause of morbidity. Our patient was followed for several years as a glass child - osteogenesis imperfecta and he had joint deformities due to skeletal fractures. We wanted to present this case to raise awareness of GD's skeletal involvement and effects of late diagnosis.

    Gaucher's disease (GD)
    DIAGNOSIS

 is a rare disease characterized by a

    β-glucocerebroside accumulation in the reticulo-endothelial system
    MICROSCOPIC

. Patients may refer to the clinic with complaints of

    bone pain
    SYMPTOMS

,

    hepatosplenomegaly
    SYMPTOMS

,

    anemia
    BIOCHEMICAL

,

    thrombocytopenia
    BIOCHEMICAL

,

    growth retardation
    SYMPTOMS

,

    interstitial pulmonary disease
    SYMPTOMS

,

    pulmonary hypertension
    SYMPTOMS

, and

    skeletal disorders
    SYMPTOMS

.

    Skeletal system involvement
    SYMPTOMS

 is observed commonly in

    Gaucher
    DIAGNOSIS

 patients and a significant cause of morbidity. Our patient was followed for several years as a

    glass child - osteogenesis imperfecta
    DIAGNOSIS

 and

    he
    GENDER

 had

    joint deformities due to skeletal fractures
    SYMPTOMS

. We wanted to present this case to raise awareness of

    GD's skeletal involvement
    SYMPTOMS

 and effects of late diagnosis.

Gaucher's disease (GD)
Gaucher
glass child - osteogenesis imperfecta


Multiple intracranial aneurysms in a patient with type I Gaucher disease: a case report and literature review.

Multiple intracranial aneurysms (IAs) have never been reported in a patient with Gaucher disease (GD). A 69-year-old-female with type I GD presented with a left sixth nerve palsy due to a large posterior inferior cerebellar artery (PICA) aneurysm. Cerebral angiography demonstrated fifteen unruptured IAs (UIAs).

    Multiple intracranial aneurysms (IAs)
    SYMPTOMS

 have never been reported in a patient with

    Gaucher disease (GD)
    DIAGNOSIS

. A

    69-year-old
    AGE

-

    female
    GENDER

 with

    type I GD
    DIAGNOSIS

 presented with a

    left sixth nerve palsy
    SYMPTOMS

 due to a

    large posterior inferior cerebellar artery (PICA) aneurysm
    SYMPTOMS

.

    Cerebral angiography
    PARACLINICAL

 demonstrated

    fifteen unruptured IAs (UIAs)
    SYMPTOMS

.


Progressive myoclonic epilepsy and horizontal gaze palsy: a rare aetiology.

Gaucher's disease is a rare autosomal recessive, potentially fatal disorder but most common type among lysosomal storage disorders. The disease's incidence is around 1/40 000 to 1/60 000 births in the general population. A 32-year-old man, born out of non-consanguineous union, presented with generalised tonic-clonic seizures and myoclonus since 17 years of age. Seizures were noted to be resistant to multiple epileptic drugs. He developed gait imbalance, intentional tremor and dysarthria. Detailed examination revealed hepatosplenomegaly, bilateral pancerebellar signs with normal power, reflexes and sensory system. He had major cognitive impairment with impaired frontal and temporal lobar functions. Bone marrow evaluation revealed Gaucher cells, confirming the diagnosis.

    Gaucher's disease
    DIAGNOSIS

 is a

    rare autosomal recessive
    GENETICS

, potentially fatal disorder but most common type among

    lysosomal storage disorders
    DIAGNOSIS

. The disease's incidence is around 1/40 000 to 1/60 000 births in the general population. A

    32-year-old
    AGE

    man
    GENDER

,

    born out of non-consanguineous union
    FAMILY

, presented with

    generalised tonic-clonic seizures
    SYMPTOMS

 and

    myoclonus
    SYMPTOMS

    since 17 years of age
    AGE

.

    Seizures were noted to be resistant to multiple epileptic drugs
    NEG_FINDINGS

.

    He
    GENDER

 developed

    gait imbalance
    SYMPTOMS

,

    intentional tremor
    SYMPTOMS

 and

    dysarthria
    SYMPTOMS

.

    Detailed examination
    PARACLINICAL

 revealed

    hepatosplenomegaly
    SYMPTOMS

,

    bilateral pancerebellar signs
    SYMPTOMS

 with

    normal power, reflexes and sensory system
    NEG_FINDINGS

.

    He
    GENDER

 had

    major cognitive impairment
    SYMPTOMS

 with

    impaired frontal and temporal lobar functions
    SYMPTOMS

.

    Bone marrow evaluation
    PARACLINICAL

 revealed

    Gaucher cells
    MICROSCOPIC

, confirming the diagnosis.

Gaucher's disease
lysosomal storage disorders


Thalassaemia Trait with Gaucher Disease: A Diagnostic Dilemma.

Gaucher Disease is an autosomal recessive disease caused by the accumulation of glucocerebrosidase due to deficiency in lysosomal glucocerebrosidase. Thalassaemia trait is asymptomatic and is usually an incidental diagnosis. Both thalassaemia and Gaucher disease can have similar haematologic manifestations and hence, their coexistence causes diagnostic dilemma. Our patient presented at one-and-a-half years with weakness, pallor, failure to thrive and massive hepatosplenomegaly. Clinical examination and history pointed to a lipid storage disease. Peripheral smear revealed microcytic hypochromic cells and nucleated red cells with haemolytic blood picture. Thalassaemia trait was indicated on haemoglobin variant analysis using High Performance Liquid Chromatography. Liver biopsy, bone marrow aspirate and therapeutic splenectomy revealed Gaucher-like cells. Type 1 Gaucher disease can be clinically asymptomatic as well as present with massive liver and spleen enlargement and involvement of bone marrow. Anaemia, splenomegaly and thrombocytopenia are the usual presentations at diagnosis, similar to the haemoglobinopathies. Gaucher-like cells with normal beta-glucocerebrosidase (pseudo-Gaucher cells) are seen in thalassaemia, leukaemia, mycobacterial infections and myeloma. Gaucher disease coexisting with thalassaemia trait is uncommon. We report the occurrence of thalassaemia trait and Gaucher disease in a child, which resulted in confusion regarding the haematological diagnosis. This report highlights the necessity of independent establishment of the diagnosis in every patient so that appropriate management decisions are taken.

    Gaucher Disease
    DIAGNOSIS

 is an

    autosomal recessive disease
    GENETICS

 caused by the

    accumulation of glucocerebrosidase
    MICROSCOPIC

 due to

    deficiency in lysosomal glucocerebrosidase
    BIOCHEMICAL

.

    Thalassaemia trait
    DIAGNOSIS

 is

    asymptomatic
    NEG_FINDINGS

 and is usually an incidental diagnosis. Both

    thalassaemia
    DIAGNOSIS

 and

    Gaucher disease
    DIAGNOSIS

 can have similar

    haematologic manifestations
    BIOCHEMICAL

 and hence, their coexistence causes diagnostic dilemma. Our patient presented

    at one-and-a-half years
    AGE

 with

    weakness
    SYMPTOMS

,

    pallor
    SYMPTOMS

,

    failure to thrive
    SYMPTOMS

 and

    massive hepatosplenomegaly
    SYMPTOMS

.

    Clinical examination and history
    PARACLINICAL

 pointed to a

    lipid storage disease
    DIAGNOSIS

.

    Peripheral smear
    PARACLINICAL

 revealed

    microcytic hypochromic cells and nucleated red cells with haemolytic blood picture
    MICROSCOPIC

.

    Thalassaemia trait
    DIAGNOSIS

 was indicated on

    haemoglobin variant analysis using High Performance Liquid Chromatography
    PARACLINICAL

.

    Liver biopsy
    PARACLINICAL

,

    bone marrow aspirate
    PARACLINICAL

 and

    therapeutic splenectomy
    MEDICATION

 revealed

    Gaucher-like cells
    MICROSCOPIC

.

    Type 1 Gaucher disease
    MICROSCOPIC

 can be

    clinically asymptomatic
    NEG_FINDINGS

 as well as present with

    massive liver and spleen enlargement
    SYMPTOMS

 and

    involvement of bone marrow
    MICROSCOPIC

.

    Anaemia
    BIOCHEMICAL

,

    splenomegaly
    SYMPTOMS

 and

    thrombocytopenia
    BIOCHEMICAL

 are the usual presentations at diagnosis, similar to the

    haemoglobinopathies
    DIAGNOSIS

.

    Gaucher-like cells
    MICROSCOPIC

 with

    normal beta-glucocerebrosidase
    NEG_FINDINGS

 (

    pseudo-Gaucher cells)
    MICROSCOPIC

 are seen in

    thalassaemia
    DIAGNOSIS

,

    leukaemia
    DIAGNOSIS

,

    mycobacterial infections
    DIAGNOSIS

 and

    myeloma
    DIAGNOSIS

.

    Gaucher disease coexisting with thalassaemia trait
    DIAGNOSIS

 is uncommon. We report the

    occurrence of thalassaemia trait and Gaucher disease
    DIAGNOSIS

 in a

    child
    AGE

, which resulted in confusion regarding the

    haematological diagnosis
    PARACLINICAL

. This report highlights the necessity of independent establishment of the diagnosis in every patient so that appropriate management decisions are taken.

asymptomatic
clinically asymptomatic
normal beta-glucocerebrosidase

weakness
pallor
failure to thrive
massive hepatosplenomegaly
massive liver and spleen enlargement
splenomegaly


Corrective surgery for kyphosis in a case of Gaucher's disease without history of vertebral compression fractures.

Gaucher's disease is a congenital metabolic disorder characterized by the accumulation of glucocerebroside in the reticuloendothelial system. Its clinical manifestations include splenomegaly, osteopenia, and pathological fractures. Cases of patients with kyphotic deformities caused by pathological vertebral compression fractures associated with Gaucher's disease are well reported. However, there has been no report regarding surgical treatment of kyphotic deformity caused by Gaucher's disease without compression fractures. In the present report, we describe surgical treatment for kyphotic deformity caused by Gaucher's disease without a past history of vertebral compression fractures.

The patient was diagnosed with Gaucher's disease at the age of 15 months. The patient was a 10-year-old girl with progressive kyphosis (84° between T6 and L3, with T12 as the apical vertebra) without compression fractures. Although the patient had been treated using a brace since the age of 3 years, the kyphosis progressed to the point where corrective surgery was required. We initially performed T3-L3 posterior spinal fusion, followed by anterior fusion 3 months later, which corrected the kyphosis to 35°. Postoperatively, the patient suffered fractures of the upper and lower extremities but did not have spinal fractures.

Two-stage anterior/posterior combined correction and fusion was performed in a patient with kyphotic deformity caused by Gaucher's disease without compression fractures. Because of bone fragility in Gaucher's disease, careful selection of the fusion range and postoperative therapy was necessary.

    Gaucher's disease
    DIAGNOSIS

 is a

    congenital metabolic disorder
    GENETICS

 characterized by the

    accumulation of glucocerebroside in the reticuloendothelial system
    MICROSCOPIC

. Its clinical manifestations include

    splenomegaly
    SYMPTOMS

,

    osteopenia
    SYMPTOMS

, and

    pathological fractures
    SYMPTOMS

. Cases of patients with

    kyphotic deformities
    SYMPTOMS

 caused by

    pathological vertebral compression fractures
    SYMPTOMS

 associated with

    Gaucher's disease
    DIAGNOSIS

 are well reported. However, there has been no report regarding

    surgical treatment of kyphotic deformity
    MEDICATION

 caused by

    Gaucher's disease
    DIAGNOSIS

    without compression fractures
    NEG_FINDINGS

. In the present report, we describe

    surgical treatment for kyphotic deformity
    MEDICATION

 caused by

    Gaucher's disease
    DIAGNOSIS

    without a past history of vertebral compression fractures
    NEG_FINDINGS

.

The patient was diagnosed with

    Gaucher's disease
    DIAGNOSIS

 at the

    age of 15 months
    AGE

. The patient was a

    10-year-old
    AGE

    girl
    GENDER

 with

    progressive kyphosis (84° between T6 and L3, with T12 as the apical vertebra)
    SYMPTOMS

    without compression fractures
    NEG_FINDINGS

. Although the patient had been

    treated using a brace
    MEDICATION

    since the age of 3 years
    AGE

, the

    kyphosis
    SYMPTOMS

 progressed to the point where

    corrective surgery
    MEDICATION

 was required. We initially performed

    T3-L3 posterior spinal fusion, followed by anterior fusion 3 months later
    MEDICATION

, which

    corrected the kyphosis to 35°
    SYMPTOMS

. Postoperatively, the patient suffered

    fractures of the upper and lower extremities
    SYMPTOMS

 but

    did not have spinal fractures
    NEG_FINDINGS

.

    Two-stage anterior/posterior combined correction and fusion
    MEDICATION

 was performed in a patient with

    kyphotic deformity
    MEDICATION

 caused by

    Gaucher's disease
    DIAGNOSIS

    without compression fractures
    NEG_FINDINGS

. Because of

    bone fragility
    SYMPTOMS

 in

    Gaucher's disease
    DIAGNOSIS

, careful selection of the fusion range and

    postoperative therapy
    MEDICATION

 was necessary.

Gaucher's disease
Gaucher's disease
Gaucher's disease
Gaucher's disease
Gaucher's disease
Gaucher's disease
Gaucher's disease


[Progressive pulmonary hypertension in a patient with type 1 Gaucher disease].

Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.

    Gaucher disease
    DIAGNOSIS

 is the most common form of

    hereditary
    GENETICS

    enzymopathies
    DIAGNOSIS

 combined into a group of

    lysosomal storage diseases
    DIAGNOSIS

. The basis for the disease is a

    hereditary
    GENETICS

    deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids
    BIOCHEMICAL

, which results in the

    accumulation of nonutilized cellular metabolism products in the macrophage lysosomes
    MICROSCOPIC

. The main clinical manifestations of

    type 1 Gaucher disease
    DIAGNOSIS

 are

    cytopenia
    BIOCHEMICAL

,

    hepatomegaly
    SYMPTOMS

, and

    splenomegaly
    SYMPTOMS

, and

    bone lesion
    SYMPTOMS

. One of the atypical clinical manifestations of

    Gaucher disease
    DIAGNOSIS

 is

    damage to the lungs
    SYMPTOMS

 with the development of

    pulmonary hypertension
    SYMPTOMS

, which is usually considered within the underlying disease - the development of

    pneumosclerosis
    DIAGNOSIS

 due to

    macrophage dysfunction
    MICROSCOPIC

. The paper describes a case of

    progressive pulmonary hypertension
    SYMPTOMS

 in a patient with

    type 1 Gaucher disease
    DIAGNOSIS

.

Gaucher disease
enzymopathies
lysosomal storage diseases
type 1 Gaucher disease
Gaucher disease
pneumosclerosis
type 1 Gaucher disease

hepatomegaly
splenomegaly
bone lesion
damage to the lungs
pulmonary hypertension
progressive pulmonary hypertension


Type 2 Gaucher disease in an infant despite a normal maternal glucocerebrosidase gene.

Gaucher disease (GD) is a recessively inherited autosomal lysosomal storage disease, the most severe of which is type 2, an acute neuronopathic form. We report an affected infant who inherited one mutant allele, Arg257Gln (c.887G>A; p.Arg296Gln) from his father, while the second, Gly202Arg (c.721G>A; p.Gly241Arg) arose by either maternal germline mosaicism or as a de novo mutation. This is the first time mutation Gly202Arg has been reported to be inherited non-traditionally. This report is part of a growing literature suggesting that GD can be inherited via germline or de novo mutations, and emphasizes that it is critical for clinicians to consider such inheritance when making diagnostic decisions or providing genetic counseling.

    Gaucher disease (GD)
    DIAGNOSIS

 is a

    recessively inherited
    GENETICS

    autosomal lysosomal storage disease
    DIAGNOSIS

, the most severe of which is

    type 2, an acute neuronopathic form
    DIAGNOSIS

. We report an affected

    infant
    AGE

 who

    inherited one mutant allele, Arg257Gln (c.887G>A; p.Arg296Gln) from his father, while the second, Gly202Arg (c.721G>A; p.Gly241Arg) arose by either maternal germline mosaicism or as a de novo mutation
    GENETICS

. This is the first time

    mutation Gly202Arg
    GENETICS

 has been reported

    to be inherited non-traditionally
    GENETICS

. This report is part of a growing literature suggesting that

    GD
    DIAGNOSIS

 can be

    inherited via germline or de novo mutations
    GENETICS

, and emphasizes that it is critical for clinicians to consider such inheritance when making diagnostic decisions or providing

    genetic counseling
    MEDICATION

.

Gaucher disease (GD)
autosomal lysosomal storage disease
type 2, an acute neuronopathic form
GD