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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
Familial hypoalphalipoproteinemias.
The familial hypoalphalipoproteinemias are a heterogeneous group of rare lipoprotein disorders characterized by extremely low levels of plasma high density lipoproteins (HDL) and, in most cases, autosomal recessive inheritance. Most of these conditions present distinctive and diagnostic clinical and laboratory abnormalities. In spite of the marked reductions in HDL, however, many of these conditions are not associated with premature atherosclerosis. This is true of Tangier disease, Fish Eye disease, lecithin: cholesterol acyltransferase deficiency, and of some variants of apo Al. Another condition, defined as a primary and familial decrease in HDL-cholesterol levels in the absence of other lipoprotein abnormalities. that is associated with premature atherosclerosis was originally called Familial Hypoalphalipoproteinemia but is better referred as to Familial Isolated Hypoalphalipoproteinemia. At present, the prevalence, inheritance, and the underlying defect(s) in this disorder are unknown. Decreased or absent synthesis of apo A-I due to a gene defect is the cause of apo A-I/C-III and apo A-I/C-III/A-IV deficiency. However, the etiology of the low levels of HDL is unclear for most of the remaining familial hypoalphalipoproteinemias. Increased catabolism, decreased synthesis and altered equilibration of HDL between intra- and extravascular spaces have all been suggested as underlying causes of low plasma HDL. Whatever their causes, these disorders are associated with altered HDL composition and altered equilibration of cholesterol amongst the various lipoprotein classes. The absence of consistent correlation with premature atherosclerosis in many of these conditions suggests that the protective effect of HDL may reside in a quantitatively small, but metabolically active subfraction of HDL particles.
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