Gaucher Disease Flashcards
What is the gene and mode of inheritance of Gaucher Disease?
GBA (AR)
What is the AJ carrier frequency of Gaucher Disease?
~1/18 (Type I)
What is the mechanism of Gaucher Disease?
Deficient glucocerebrosidase (glucosylceramidase) enzyme activity
Which variant is the most common in Gaucher Disease?
Asn409Ser
(29% of affected individuals will be homozygous)
60% of individuals will be compound het with this variant
What are the most common Gaucher variants?
Asn409Ser (formerly known as p.N370S)
Leu483Pro
c.84dupG
c.115+1G>A
What is a known genotype/phenotype association with Gaucher Disease?
Asn409Ser (formerly known as p.N370S) with Type I non-neuronopathic
What is the phenotype of untreated Gaucher Type I?
Bone disease
Hepatosplenomegaly
Anemia and thrombocytopenia
Lung disease
Absence of primary CNS disease
What is the bone disease in Gaucher Type I?
Osteopenia
Focal lytic or sclerotic lesions
Osteonecrosis
What is the phenotype of Gaucher Type II?
Type II if onset < 2years, rapidly progressive, lethal neurodegeneration by age 2-4 years
FTT, minimal development, hepatosplenomegaly, spasticity, opisthotonus
What is the phenotype of Gaucher Type III?
Children at any age with more slowly progressive neurodegeneration but death by 20-30 years
Dysphagia, nystagmus, DD, hepatosplenomegaly, cyopenias, seizures, spasticity, ataxia, dementia
What are the characteristics of the cardiovascular form of Gaucher Disease?
Calcification of the aortic and mitral valves
mild splenomegaly
corneal opacities
Supranuclear ophthalmoplegia
What is the perinatal-lethal form of Gaucher Disease?
The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis
What does a bone marrow biopsy show in Gaucher Disease?
“Gaucher cells”
Is glucocerebrosidase enzyme activity used to identify carriers of Gaucher?
No, glucocerebrosidase enzyme activity in peripheral blood leukocytes is unreliable for carrier determination because of significant overlap in residual enzyme activity levels between obligate carriers and the general (non-carrier) population
What prenatal testing is performed in Gaucher Disease?
Molecular testing
Glucocerebrosidase enzyme activity on amnio/CVS
What other tests might be run in Gaucher Disease?
Plasma chitotriosidase levels (correlates with disease activity), blood counts, liver function, liver/spleen imaging, skeletal imaging and bone density, pulmonary/cardiac assessment
Which types of Gaucher can enzyme replacement therapy be used?
Types I and III
What are the treatments in Gaucher Types I and III?
IV enzyme replacement therapy (ERT)
Oral substrate reduction therapy (SRT)
Bone Marrow Transplant (questionable risk/benefit)
What are the differential diagnoses for Gaucher Disease?
Saposin C Deficiency
Other LSDs
Legg-Calve-Perthes Disease
What should you avoid in Gaucher Disease?
Nonsteroidal anti-inflammatory drugs (with mod to severe thrombocytopenia)
What is the pregnancy management in Gaucher Disease?
Eval by hematologist to assess bleeding
Pregnancy may exacerbate preexisting symptoms like bone pain
Eliglustat is not contraindicated
What is the risk of someone with Gaucher Disease developing Parkinson Disease?
20- to 30-fold the risk to an individual in the general population
What is the risk of Parkinson by 60 and 80 years in Gaucher Disease and carriers?
4.7% and 9.1% among those with GD,
1.5% and 7.7% among heterozygotes
0.7% and 2.1% among non-carriers, respectively
