Garber genetics of dyslipidemia

Question 1

What defects are seen in familial hyperchylomicronemia

Answer 1

1. lipoprotein lipase (can’t break it down
2. LPL’s cofactor apoC-II

SINGLE GENE DYSLIPIDEMIA

Question 2

For Hyperchylomicronemia, describe:

a. inheritance pattern
b. when presentation occurs and symptoms
c. classic sign clinically

Answer 2

1. autosomal recessive
2. pediatric; abdominal pain due to pancreatitis; hepatoplenomegaly (pancreas, spleen, and liver take up these chylomicrons); eruptic xanthomas

• we see elevated TG’s (even with fasting) and decreased LDL

Question 3

what is a good treatment for Familial hyperchylomicronemia

Answer 3

• FAT FREE DIET

Question 4

Name two physical signs that serve as clues for rare lipid disorders

Answer 4

1. xanthomas

2. corneal arcus (cholesterol deposits at eye)

Question 5

what are genetics red flags for these dyslipidemias

Answer 5

1. extreme/unusual lab values
2. family history
3. early onset compared to gen pop

Question 6

what is the most common hereditary dyslipidemia

What marker is elevated? inheritance pattern?

Answer 6

• Familial hypercholesterolemia
• autosomal dominant

HIgh LDL levels

Question 7

Familial hypercholesterolemia is caused by defects in _____________, but is most commonly caused by mutations in __________

what are less common mutations

Answer 7

• LDLR production, presentaiton, or trafficking

most commonly caused mutaiont in LDLR

less common: APOB, PCSK9, ARH

Question 8

T/F there is a single gene mutation in the LDLR that causes FH, and we manage patients based on that one mutation

Answer 8

F… many different mutations (it’s not a single gene)

• we do NOT manage differently based on mutation

Question 9

what is cascade testing for Familial hypercholesterolemia?

Answer 9

it’s a way to do risk evaluation for families based on:

• index case and identification
• start with affected individual and move out from family and see risk based on their relation to family

Question 10

what is benefit of cascade testing

Answer 10

• increased treatment rates and improves lipid profiles

- reduces CHD mortality

Question 11

what is the result of a pt with 2 mutant LDLR alleles?

Answer 11

• Severe disease
• LDL level above 700 mg/dL
• significant coronary artery disease in childhood

point is you can inherited mutations from both parents if they both have mutations

Question 12

What are the two defects seen in dyslipidemia

Answer 12

1. single gene

2. common forms (enzyme impairment, but combine with other factors to determine actual LDL levels)

Question 13

T/F genetic testing is useful for risk analysis of common forms of dyslipidemia

Answer 13

F, not highly predictive of conditions like cardiovascular disease

In fact, Family history was more predictive htan genetic tests with the general populaiton

Question 14

so who is genetic testing good for?

Answer 14

• those with single gene mutations, or those that “fall off curve” –> have very high LDL levels

Question 15

why does screening matter if you know that a defect is present for dyslipidemias?

Answer 15

1. reccurence risks differ
2. early screening may be needed
3. aggressive management needed
4. improves outcomes