DISORDERS OF LIPIDS AND LIPOPROTEIN METABOLISM

Question 1

DISORDERS OF LIPIDS AND LIPOPROTEIN METABOLISM

Answer 1

There are several rare, inherited metabolic diseases associated with the accumulation of lipids in tissues, and others in which plasma lipoprotein concentrations are reduced.
Secondary lipid disorders are those arising as a consequence of a disease, drug treatment, or defective nutrition.
The commonest disorders are the hyperlipidaemias.

Question 2

Classification of the disorders

Answer 2

1. Fredrickson Classification: Type I -V
2. Diagnostic/Genetic Classification: Primary (Familial) or Secondary (Acquired) disorders
3. Based on type of lipid predominantly elevated: Hypercholesterolaemia, Hypertriglyceridaemia, elevated/low HDL-C

Question 3

Fredrickson Classification Type 1

Answer 3

Type 1 is associated with marked hyperchylomicronaemia. It is caused by a deficiency of lipoprotein lipase or a deficiency of its activator, apoprotein C2.

Symptoms: Xanthoma
Treatment: increase TAGs

Question 4

Fredrickson Classification Type 2

Answer 4

Type 2a implies hypercholesterolaemia without hypertriglyceridaemia and includes monogenic inherited disorders, such as familial hypercholesterolaemia, but is more often polygenic in origin

Type 2b implies combined hypercholesterolaemia with increased amounts of circulating TGs. It is the pattern seen in familial combined dyslipidaemia, but there are several other causes, including 20 hyperlipidaemia associated with the overproduction of VLDL.

Question 5

Fredrickson Classification Type 3

Answer 5

Type 3 lipid disorder is associated with variants of apoE protein, which leads to an accumulation of abnormal IDL particles.

This disorder may be suspected when cholesterol and TGs increase in equimolar amounts, reflecting the cholesterol enrichment of IDL.

Question 6

Fredrickson Classification Type 4

Answer 6

Type 4 is associated with hypertriglyceridaemia that implies increases in VLDL without chylomicrons.

Question 7

Fredrickson Classification Type 5

Answer 7

Type 5 is associated with marked hypertriglyceridaemia and increased VLDL and chylomicrons. The primary cause may be increases in VLDL and IDLs that interfere with the receptor-mediated removal of chylomicrons.