Hypolipoproteinaemias

For a review of hypolipoproteinaemia see reference [Durrington, 1995a].

The problem of hypolipoproteinaemia

Hypolipoproteinaemia is increasing as a clinical problem as screening for high cholesterol has caused more cases to be discovered. People who have had low serum cholesterol levels all their lives do not seem to be at any disadvantage unless the decrease is profound, as in abetalipoproteinaemia. Indeed, their relative freedom from cardiovascular disease may lead to longevity. When the condition is first discovered it is often difficult to be sure that the low cholesterol is not due to an acquired disease such as malignancy (eg, colonic or prostatic neoplasms, leukaemia, reticulosis or myeloma) or malabsorption (due, for example, to a short bowel, blind-loop syndrome, coeliac disease, pancreatic exocrine insufficiency or giardiasis).

Heterozygous familial hypobetalipoproteinaemia and abetalipoproteinaemia
Some people with serum cholesterol levels around 1.0-3.5 mmol/L (40-140 mg/dL) will have heterozygous familial hypobetalipoproteinaemia, an autosomal dominant condition in which truncated apo B mutations have been described. This condition is benign, but the homozygous version of the disorder and abetalipoproteinaemia (inherited as an autosomal recessive and producing more profound hypocholesterolaemia) are associated with the following:

retinitis pigmentosa;
unusually shaped erythrocytes (acanthocytes);
a syndrome resembling Friedreich's ataxia (preventable with fat-soluble vitamin administration);
steatorrhoea (which can create diagnostic confusion with other causes of malabsorption leading to secondary hypocholesterolaemia); and
fatty liver.

Mutation of the MTP gene rather than of the apo B gene is associated with abetalipoproteinaemia.

Analphalipoproteinaemia
Analphalipoproteinaemia (Tangier disease) is a very rare disorder in which HDL is virtually absent due to:

rapid clearance;
reduced LDL cholesteryl ester; and
cholesteryl ester deposition throughout the body.

Symptoms of analphalipoproteinaemia
Analphalipoproteinaemia leads to:

enlarged, orange-yellow tonsils and adenoids;

lymph node enlargement;

hepatosplenomegaly;

bone marrow infiltration (thrombocytopenia);

orange-brown spots on the rectal mucosa;

neuropathy; and

corneal cloudiness. It has recently been ascribed to mutation of the ATP-binding cassette-A1 (ABCA1) gene encoding the cholesterol efflux regulatory protein.

Fish eye disease
Fish eye disease is another rare condition, which has extremely low levels of HDL caused by deficiency of alpha-LCAT activity. The only symptoms are corneal opacities and there is no premature CHD [Carlson, 1982].