Diagnosis and treatment of high density lipoprotein deficiency

Abstract

Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors.

Keywords: Genetic dyslipidemias; HDL; HDL-C; High-density lipoproteins; Lipoproteins.

Figure 1

Two dimensional gel electrophoresis patterns of HDL particles from a normal subject (far left) and a patient with premature coronary heart disease (CHD) (second from left) along with two depictions of the position (middle right) and the potential structure (far right) of apoA-I containing HDL particles are shown. On the gel patterns the particle size in nm (diameter) is plotted on the vertical axis and the electrophoretic mobility (preβ, α, and preα) is plotted on the horizontal axis. The CHD patient clearly has a marked reduction in the apoA-I concentration in very large α-1 HDL.

Figure 2

Two dimensional gel electrophoretic patterns of apoA-I containing HDL particles (from left to right) are shown from a control subject, an apoA-I deficient patient (no particles), a TD patient (only preβ-1 HDL), an FLD patient (preβ-1 and α-4 HDL, with some larger discoidal fusion particles), a LPL deficient patient with lack of large α HDL, an HL deficient patient with decrease in α-2 HDL, and a patient with CETP deficiency with an excess of abnormal very large HDL particles.

Figure 3

Images of corneal arcus and corneal opacification are shown. In the upper left is a patient with homozygous apolipoprotein A-I deficiency with somewhat atypical arcus juvenilis. In the upper right panel is a patient with homozygous TD showing diffuse corneal opacification only seen by slit lamp examination. In the lower left panel is a patient with homozygous FLD with marked corneal arcus juvenilis and corneal opacification. In the lower right panel is a young patient with compound heterozygous FED with marked arcus juvenilis and some diffuse corneal opacification.