Gaucher Disease

Question 1

What is the gene and mode of inheritance of Gaucher Disease?

Answer 1

GBA (AR)

Question 2

What is the AJ carrier frequency of Gaucher Disease?

Answer 2

~1/18 (Type I)

Question 3

What is the mechanism of Gaucher Disease?

Answer 3

Deficient glucocerebrosidase (glucosylceramidase) enzyme activity

Question 4

Which variant is the most common in Gaucher Disease?

Answer 4

Asn409Ser
(29% of affected individuals will be homozygous)

60% of individuals will be compound het with this variant

Question 5

What are the most common Gaucher variants?

Answer 5

Asn409Ser (formerly known as p.N370S)
Leu483Pro
c.84dupG
c.115+1G>A

Question 6

What is a known genotype/phenotype association with Gaucher Disease?

Answer 6

Asn409Ser (formerly known as p.N370S) with Type I non-neuronopathic

Question 7

What is the phenotype of untreated Gaucher Type I?

Answer 7

Bone disease
Hepatosplenomegaly
Anemia and thrombocytopenia
Lung disease
Absence of primary CNS disease

Question 8

What is the bone disease in Gaucher Type I?

Answer 8

Osteopenia
Focal lytic or sclerotic lesions
Osteonecrosis

Question 9

What is the phenotype of Gaucher Type II?

Answer 9

Type II if onset < 2years, rapidly progressive, lethal neurodegeneration by age 2-4 years

FTT, minimal development, hepatosplenomegaly, spasticity, opisthotonus

Question 10

What is the phenotype of Gaucher Type III?

Answer 10

Children at any age with more slowly progressive neurodegeneration but death by 20-30 years

Dysphagia, nystagmus, DD, hepatosplenomegaly, cyopenias, seizures, spasticity, ataxia, dementia

Question 11

What are the characteristics of the cardiovascular form of Gaucher Disease?

Answer 11

Calcification of the aortic and mitral valves
mild splenomegaly
corneal opacities
Supranuclear ophthalmoplegia

Question 12

What is the perinatal-lethal form of Gaucher Disease?

Answer 12

The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis

Question 13

What does a bone marrow biopsy show in Gaucher Disease?

Answer 13

“Gaucher cells”

Question 14

Is glucocerebrosidase enzyme activity used to identify carriers of Gaucher?

Answer 14

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

Question 15

What prenatal testing is performed in Gaucher Disease?

Answer 15

Molecular testing
Glucocerebrosidase enzyme activity on amnio/CVS

Question 16

What other tests might be run in Gaucher Disease?

Answer 16

Plasma chitotriosidase levels (correlates with disease activity), blood counts, liver function, liver/spleen imaging, skeletal imaging and bone density, pulmonary/cardiac assessment

Question 17

Which types of Gaucher can enzyme replacement therapy be used?

Answer 17

Types I and III

Question 18

What are the treatments in Gaucher Types I and III?

Answer 18

IV enzyme replacement therapy (ERT)
Oral substrate reduction therapy (SRT)
Bone Marrow Transplant (questionable risk/benefit)

Question 19

What are the differential diagnoses for Gaucher Disease?

Answer 19

Saposin C Deficiency
Other LSDs
Legg-Calve-Perthes Disease

Question 20

What should you avoid in Gaucher Disease?

Answer 20

Nonsteroidal anti-inflammatory drugs (with mod to severe thrombocytopenia)

Question 21

What is the pregnancy management in Gaucher Disease?

Answer 21

Eval by hematologist to assess bleeding
Pregnancy may exacerbate preexisting symptoms like bone pain
Eliglustat is not contraindicated

Question 22

What is the risk of someone with Gaucher Disease developing Parkinson Disease?

Answer 22

20- to 30-fold the risk to an individual in the general population

Question 23

What is the risk of Parkinson by 60 and 80 years in Gaucher Disease and carriers?

Answer 23

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