Monogenic hypercholesterolemia

Rader DJ, Cohen J, Hobbs HH Monogenic hypercholesterolemia new insights in pathogenesis and treatment./ Clin Invest 111 1795-1803,2003-... 

For ethical reasons, children enrolled in these clinical trials have also received standard therapy of enzyme infusions, so the results of these studies have been difficult to interpret and are controversial. Nevertheless, there is some evidence that the ex vivo gene transfer approach may evoke a biological response relevant to the treatment of ADA deficiency. Such interpretations have stimulated efforts to use the ex vivo strategy for other monogenic disorders, such as familial hypercholesterolemia, hemophilia B, and Gaucher s disease. 

Monogenic dyslipoproteinemias can generally be grouped into five categories (1) hypertriglyceridemia with an increase in chylomicrons and the clinical sign of pancreatitis, (2) mixed hyperlipidemia with an increase in chylomicron and VLDL remnants and an increased risk of premature atherosclerosis, (3) hypercholesterolemia with an increase in LDL and an increased risk for premature atherosclerosis, (4) hypoalphalipoproteinemia with low HLD and an increased risk for premature atherosclerosis, and (5) hypolipoproteinemia with a decrease in VLDL and LDL, which may lead to neurological disease. 

Schrott HG, Goldstein JL, Hazzard WR. Familial hypercholesterolemia in a large kindred Evidence for a monogenic mechanism. Ann Intern Med 1971 711-20. 

Familial homozygous hypercholesterolemia is a rare hereditary monogenic disorder caused by mutations of the LDL receptor gene. Individuals have severe hypercholesterolemia associated with premature atherosclerosis. In a single study, patients were treated with gene therapy... 

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