Hypoalphalipoproteinemia

Scanu, A. M., Edelstein, C., Fless, G. M., Eisenbart, J., Sitrin, M., Kasawa, B., and Hinman, J., Postprandial lipoprotein(a) response to a single meal containing either saturated or w-3 polyunsaturated fatty acids in subjects with hypoalphalipoproteinemia. Metab., Clin. Exp. 41, 1361-1366 (1992). 

High-density lipoproteins (HDL) exert several ant/atherogenic effects. They participate in retrieval of cholesterol from the artery wall and inhibit the oxidation of atherogenic lipoproteins. Low levels of HDL (hypoalphalipoproteinemia) are an independent risk factor for atherosclerotic disease and thus are a target for intervention. 

Rare genetic disorders, including Tangier disease and LCAT (lecithin cholesterol acyltransferase) deficiency, are associated with extremely low levels of HDL. Familial hypoalphalipoproteinemia is a more common disorder with levels of HDL cholesterol usually below 35 mg/dL in men and 45 mg/dL in women. These patients tend to have premature atherosclerosis, and the low HDL may be the only identified risk factor. Management should include special attention to avoidance or treatment of other risk factors. Niacin increases HDL in many of these patients. Reductase inhibitors and fibric acid derivatives exert lesser effects. 

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. 

Familial hypoalphalipoproteinemia (rare) in which the serum concentration of (protective) HDL is low. Coronary heart and peripheral vascular disease result. 

This disorder is characterized by normal plasma hpids and LDL cholesterol and reduced HDL cholesterol, below the 5th percentUc. Although patients with this disorder are clinically normal, they have a high incidence of CHD. The molecular basis of familial hypoalphalipoproteinemia is unknown. This disorder is the result of either the decreased biosynthesis or the increased catabolism of HDL or apo A-L Although the mode of transmission is not certain, in some kindreds familial hypoalphalipoproteinemia is inherited as an autosomal dominant trait. 

In homozygous familial hypoalphalipoproteinemia, only traces of HDL cholesterol are found in plasma, and apo A-I is undetectable. These patients have corneal clouding and are at increased risk for development of premature CHD. Heterozygotes exhibit no clinical signs but have about... 

Ilq23-q24 1.87 APOA1 Apolipoprotein A-I 107680 Amyloidosis, combined ApoA-I and apoC-III deficiency, corneal clouding, hypoalphalipoproteinemia, Tangier disease, systemic non-neuropathic amyloidosis... 

Familial hypoalphalipoproteinemia has been identified in several kindreds with a history of accelerated coronary disease. Plasma lipid and lipoprotein values were all normal except for reduced levels of HDL cholesterol (50% of... 

ABCAl Cholesterol, PC Familial hypoalphalipoproteinemia, Tangier disease... 

Another frequent inherited lipoprotein disorder is hypoalphalipoproteinemia. The frequency of this disorder again reflects its usefulness during evolution. The metabolic upregulation of HDL synthesis by ascorbate became an important mechanism to reverse and decrease existing lipid deposits in the vascular wall. 

LCAT deficiency in LDLr-/- mice and Apo E -/- mice fed an atherogenic diet, resulted in aortic cholesterol deposition likely caused by a reduction in plasma HDL, increased saturation of CE in apo B lipoproteins, and in the Apo E -/- background, increased plasma Apo B lipoprotein concentration (470). LCAT-deficient mice are associated with an increase in oxidative stress that is paradoxically reversed in a hyperlipidemic background possibly caused by the redistribution of paraoxonase (PON) to the non-HDL fraction. This may in part contribute to the reduced atherosclerosis seen in Apo E -/- xLCAT -/- mice (this could explain the surprising finding that LCAT-deficient subjects have severe hypoalphalipoproteinemia yet are not prone to premature CHD) (477). 

Familial hypoalphalipoproteinemia A deficiency in HDL due to mutations at the ABCAl locus. 

Tangier disease is a rare recessive disorder in which patients have almost no HDL. Cholesterol ester accumulates in macrophages and macrophage-rich tissues like spleen and liver. Familial hypoalphalipoproteinemia (FHA) is a very common dominant disorder in which people have low HDL (typically <30 mg/dl) and suffer from premature heart disease even without an elevation in LDL. 

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