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 are a significant independent risk factor for cardiovascular disease (CVD), and are 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.

A Novel Mutation in ABCA1 Gene Causing Tangier Disease in an Italian Family with Uncommon Neurological Presentation

“…Neurological symptoms represented the prevalent clinical sign in the proband. It has been reported that several different inherited defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferas (LCAT) genes may be responsible for FHD (24). Also APOA1-related amyloidosis is characterized by a small fiber neuropathy.…”

Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement

“…7 Homozygous or compound heterozygous apolipoprotein A-I deficiency has been described in less than 20 patients worldwide and is characterised by an almost Review complete deficiency of HDL cholesterol (<0·3 mmol/L or <10 mg/dL) and apolipoprotein A-I (<0·1 g/L) and, in most individuals, premature coronary heart disease. [79][80][81] Patients with two null alleles have xanthomas, either limited to the eyelids, or covering the body (figure 2). [79][80][81] Patients with homozygous or hemizygous missense mutations have residual plasma concentrations of a structurally abnormal apolipoprotein A-I, and can show corneal clouding, similar to familial LCAT deficiency and fish-eye disease.…”

“…[79][80][81] Patients with two null alleles have xanthomas, either limited to the eyelids, or covering the body (figure 2). [79][80][81] Patients with homozygous or hemizygous missense mutations have residual plasma concentrations of a structurally abnormal apolipoprotein A-I, and can show corneal clouding, similar to familial LCAT deficiency and fish-eye disease. [79][80][81] However, this feature is inconsistently observed in patients with complete apolipoprotein A-I deficiency, sometimes detectable only by slit lamp examination.…”

“…[79][80][81] Patients with homozygous or hemizygous missense mutations have residual plasma concentrations of a structurally abnormal apolipoprotein A-I, and can show corneal clouding, similar to familial LCAT deficiency and fish-eye disease. [79][80][81] However, this feature is inconsistently observed in patients with complete apolipoprotein A-I deficiency, sometimes detectable only by slit lamp examination. [79][80][81] Definitive diagnosis is made by targeted sequencing of the APOA1 gene.…”

The many ways tissue phagocytes respond to dying cells

“…Genetic deficiency for ABCA1 reduces the plasma levels of HDL cholesterol (HDL-C), one of the parameters associated with higher risk for cardiovascular disease. 150,151,167 In mouse models of atherosclerosis, macrophage-specific deletion of ABCA1 resulted in a large accumulation of cholesterol in macrophages, and exacerbated atherosclerosis in the advanced stage of disease. 168 ABCA1 also protects macrophages from undergoing apoptosis after the engulfment of apoptotic cells, and it may do so in two ways.…”