Deficiencies of
lipoproteins occur as
genetic disorders or may be presenting features of underlying disease. Familial
high density lipoprotein (HDL), or
alpha-lipoprotein, deficiency so far described includes
Tangier disease,
Lecithin: cholesterol acyltransferase (
LCAT) deficiency, A-I Variants syndrome and
Fish-eye disease. In 1981 Vergani described a familial aggregation of low
HDL-cholesterol (less than 33 mg/dl) and
Apo A (about 50% of normal levels) in the presence of normal VLDL and
LDL-cholesterol. LCAT and
lipoprotein lipase activities, both extrahepatic and hepatic, were normal. By
zonal ultracentrifugation HDL2 subclass was found to be reduced. HDL
apoproteins, examined by isoelectric focusing in
polyacrylamide gel, were qualitatively normal. No disorders to which low levels of HDL might be secondary (e.g.,
overweight, cigarette smoking, nephropathy,
liver disease) are present in the affected members. The underlying biochemical defect is unknown but probably involves altered synthesis or catabolism of HDL. Familial
hypo-alpha-lipoproteinemia is accompanied by a high prevalence of premature
myocardial infarction and
sudden death. The genetic analysis of the disorder is consistent with autosomal inheritance. The criteria for the definition of familial
hypo-alpha-lipoproteinemia are, therefore, as follows: 1) low
HDL-cholesterol level in the presence of normal VLDL and
LDL-cholesterol levels; 2) absence of diseases or factors to which
hypo-alpha-lipoproteinemia might be secondary; 3) presence of a similar
lipoprotein pattern in a first degree relative.