1-11 Gaucher's disease

Question 1

Enzymatic defect in Gaucher

Answer 1

Glucosyl Ceramide via ACID BETA-GLUCOSIDASE -> Glucose + Ceramide

Question 2

Pathophys of Gaucher

Answer 2

bone marrow->monocytes-> MACROPHAGES

Macrophages go to: liver kupffer cells, osteoclasts, alveolar macrohpages, tissue macrophages (spleen), also back to bone marrow

Question 3

Manifestations of Gaucher

Answer 3

Hepatomegaly, splenomegaly
Thrombocytopenia, anemia, leukopenia, hypersplenism (easy bruising)
Bone disease, bone pain - unusual shape/modeling (erlenmeyer flask deformity) avascular necrosis of bone with collapsed femoral heads cause bone death

Chronic pain low level ache in bones
Acute: bone infarction, requires opioids, days to weeks

Question 4

Type 1 Gaucher

Answer 4

One of most common genetic disorders (autosomal recessive)
Higher rates in ashkenazi jews
dx-ed middle age or later (but also many in 0-10 age)
extremely variable severity/rate of progression

Question 5

Gaucher in children

Answer 5

Growth retardation after 1-2yrs old

Pubertal dev freqently delayed

Question 6

Tx Guacher

Answer 6

Enzyme replacement therapy! super effective super expensive

Drug companies are incentivized to get more patients treated with their drug since insurance covers majority of cost

Question 7

Orphan Drugs

Answer 7

1983: Extra funding for diseases that afflict less than 200,000 people in US

Incentives: marketing exclusivity, grants for clinical testing, tax credits, exempt from user fees to FDA