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Differential diagnosis of familial high density lipoprotein deficiency syndromes

      Abstract

      Monogenic high density lipoprotein (HDL) deficiency, because of defects in the genes of apolipoprotein A-I (apoA-I), adenosine triphosphate binding cassette transporter A1 (ABCA1) or lecithin:cholesterol acyltransferase (LCAT), can be assumed in patients with HDL cholesterol levels below the fifth percentile within a given population. As in a first step underlying diseases should be excluded. Patients with a virtual absence of HDL must undergo careful physical examination to unravel the clinical hallmarks of certain HDL deficiency syndromes. In addition, family studies should be initiated, to demonstrate the vertical transmission of the low HDL cholesterol phenotype. Definitive diagnosis requires specialized biochemical tests and the demonstration of a functionally-relevant mutation in one of the three discussed candidate genes. As yet no routinely used drug is able to increase HDL cholesterol levels in patients with familial low HDL cholesterol so that prevention of cardiovascular disease in these patients must be focused on the avoidance and treatment of additional risk factors.

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      References

        • Gotto Jr., A.M.
        • Brinton E.A.
        Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update.
        J Am Coll Cardiol. 2004; 43: 717-724
        • Devroey D.
        • Vantomme K.
        • Betz W.
        • Vandevoorde J.
        • Kartounian J.
        A review of the treatment guidelines on the management of low levels of high-density lipoprotein cholesterol.
        Cardiology. 2004; 102: 61-66
        • Genest Jr., J.J.
        • Martin-Munley S.S.
        • McNamara J.R.
        • et al.
        Familial lipoprotein disorders in patients with premature coronary artery disease.
        Circulation. 1992; 85: 2025-2033
        • Wang X.
        • Paigen B.
        Genetics of variation in HDL cholesterol in humans and mice.
        Circ Res. 2005; 96: 27-42
        • Pocovi M.
        • Cenarro A.
        • Civeira F.
        • et al.
        Beta-glucocerebrosidase gene locus as a link for Gaucher's disease and familial hypo-alpha-lipoproteinaemia.
        Lancet. 1998; 351: 1919-1923
        • McGovern M.M.
        • Pohl-Worgall T.
        • Deckelbaum R.J.
        • et al.
        Lipid abnormalities in children with types A and B Niemann Pick disease.
        J Pediatr. 2004; 145: 77-81
        • Choi H.Y.
        • Karten B.
        • Chan T.
        • et al.
        Impaired ABCA1-dependent lipid efflux and hypoalphalipoproteinemia in human Niemann-Pick type C disease.
        J Biol Chem. 2003; 278: 32569-32577
        • Cohen J.C.
        • Kiss R.S.
        • Pertsemlidis A.
        • et al.
        Multiple rare alleles contribute to low plasma levels of HDL cholesterol.
        Science. 2004; 305: 869-872
        • Knoblauch H.
        • Bauerfeind A.
        • Toliat M.R.
        • et al.
        Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol.
        Hum Mol Genet. 2004; 13: 993-1004
        • Costanza M.C.
        • Cayanis E.
        • Ross B.M.
        • et al.
        Relative contributions of genes, environment, and interactions to blood lipid concentrations in a general adult population.
        Am J Epidemiol. 2005; 161: 714-724
        • Nauck M.
        • Marz W.
        • Jarausch J.
        • et al.
        Multicenter evaluation of a homogeneous assay for HDL-cholesterol without sample pretreatment.
        Clin Chem. 1997; 43: 1622-1629
        • Assmann G.
        • Schulte H.
        Results and conclusions of the prospective cardiovascular münster (PROCAM) study.
        in: Assmann G. Lipid Metabolism Disorders and Coronary Heart Disease. 2nd ed. MMV Medizin Verlag München, 1993: 19-67
        • Brooks-Wilson A.
        • Marcil M.
        • Clee S.M.
        • et al.
        Mutations in ABC1 in Tangier disease and familial high density lipoprotein deficiency.
        Nature Genet. 1999; 22: 336
        • von Eckardstein A.
        • Nofer J.R.
        • Assmann G
        HDL and coronary heart disease: role of cholesterol efflux and reverse cholesterol transport.
        Arterioscler Thromb Vasc Biol. 2001; 20: 13-27
        • Sorci-Thomas M.G.
        • Thomas M.J.
        The effects of altered apolipoprotein A-I structure on plasma HDL concentration.
        Trends Cardiovasc Med. 2002; 12 ([Review]): 121-128
        • Genest Jr., J.
        • Marcil M.
        • Denis M.
        • Yu L.
        High density lipoproteins in health and in disease.
        J Investig Med. 1999; 47: 31-42
        • Assmann G.
        • von Eckardstein A.
        • Funke H.
        High density lipoproteins, reverse transport of cholesterol, and coronary artery disease. Insights from mutations.
        Circulation. 1993; 87: III28-III34
        • Chiesa G.
        • Sirtori C.R.
        Apolipoprotein A-I(Milano): current perspectives.
        Curr Opin Lipidol. 2003; 14: 159-163
        • Bruckert E.
        • von Eckardstein A.
        • Funke H.
        • et al.
        The replacement of arginine by cysteine at residue 151 in apolipoprotein A-I produces a phenotype similar to that of apolipoprotein A-IMilano.
        Atherosclerosis. 1997; 128: 121-128
        • Andreola A.
        • Bellotti V.
        • Giorgetti S.
        • et al.
        Conformational switching and fibrillogenesis in the amyloidogenic fragment of apolipoprotein A-I.
        J Biol Chem. 2003; 278: 2444-2451
        • Obici L.
        • Palladini G.
        • Giorgetti S.
        • et al.
        Liver biopsy discloses a new apolipoprotein A-I hereditary amyloidosis in several unrelated Italian families.
        Gastroenterology. 2004; 126: 1416-1422
        • Joy T.
        • Wang J.
        • Hahn A.
        • Hegele R.A.
        APOA1 related amyloidosis: a case report and literature review.
        Clin Biochem. 2003; 36: 641-645
        • Miller M.
        • Aiello D.
        • Pritchard H.
        • et al.
        Apolipoprotein A-I(Zavalla) (Leu159→Pro): HDL cholesterol deficiency in a kindred associated with premature coronary artery disease.
        Arterioscler Thromb Vasc Biol. 1998; 18: 1242-1247
        • Hovingh G.K.
        • Brownlie A.
        • Bisoendial R.J.
        • et al.
        A novel apoA-I mutation (L178P) leads to endothelial dysfunction, increased arterial wall thickness, and premature coronary artery disease.
        J Am Coll Cardiol. 2004; 44: 1429-1435
        • Tall A.
        • Breslow J.L.
        • Rubin E.R.
        Gentic disorders affecting high density lipoproteins.
        in: Scriver C.R. Beaudet A.L. Sly E.S. Valle D. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. McGraw-Hill, New York2000: 2915-2936
        • Ikewaki K.
        • Matsunaga A.
        • Han H.
        • et al.
        A novel two nucleotide deletion in the apolipoprotein A-I gene, apoA-I Shinbashi, associated with high density lipoprotein deficiency, corneal opacities, planar xanthomas, and premature coronary artery disease.
        Atherosclerosis. 2004; 172: 39-45
        • Miccoli R.
        • Bertolotto A.
        • Navalesi N.
        • et al.
        Compound heterozygosity for a structural apolipoprotein A-I-Variant - ApoA-I(L141R)Pisa - and an Apolipoprotein A-I null allele in patients with density lipoprotein deficiency, corneal opacifications, and coronary heart disease.
        Circulation. 1996; 94: 1622i-1628i
        • Römling R.
        • von Eckardstein A.
        • Funke H.
        • et al.
        A nonsense mutation in the apolipoprotein A-I gene is associated with high density lipoprotein deficiency but not with coronary artery disease.
        Arterioscler Thromb. 1994; 14: 1915-1922
        • von Eckardstein A.
        • Funke H.
        • Walter M.
        • et al.
        Structural analysis of apolipoprotein A-I variants. Amino acid substitutions are nonrandomly distributed throughout the apolipoprotein A-I primary structure.
        J Biol Chem. 1990; 265: 8610-8617
        • Joyce C.
        • Freeman L.
        • Brewer Jr., H.B.
        • Santamarina-Fojo S.
        Study of ABCA1 function in transgenic mice.
        Arterioscler Thromb Vasc Biol. 2003; 23: 965-971
        • Singaraja R.R.
        • Brunham L.R.
        • Visscher H.
        • Kastelein J.J.
        • Hayden M.R.
        Efflux and atherosclerosis: the clinical and biochemical impact of variations in the ABCA1 gene.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1322-1332
        • Wang N.
        • Tall A.R.
        Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1178-1184
        • Probst M.C.
        • Thumann H.
        • Aslanidis C.
        • et al.
        Screening for functional sequence variations and mutations in ABCA1.
        Atherosclerosis. 2004; 175: 269-279
        • Frikke-Schmidt R.
        • Nordestgaard B.G.
        • Jensen G.B.
        • Tybjaerg-Hansen A.
        Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population.
        J Clin Invest. 2004; 114: 1343-1353
        • Clee S.M.
        • Kastelein J.J.
        • van Dam M.
        • et al.
        Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes.
        J Clin Invest. 2000; 106: 1263-1270
        • Kyriakou T.
        • Hodgkinson C.
        • Pontefract D.E.
        • et al.
        Genotypic effect of the -565C>T polymorphism in the ABCA1 gene promoter on ABCA1 expression and severity of atherosclerosis.
        Arterioscler Thromb Vasc Biol. 2005; 25: 418-423
        • Tregouet D.A.
        • Ricard S.
        • Nicaud V.
        • et al.
        In-depth haplotype analysis of ABCA1 gene polymorphisms in relation to plasma ApoA1 levels and myocardial infarction.
        Arterioscler Thromb Vasc Biol. 2004; 24: 775-781
        • Assmann G.
        • von Eckardstein A.
        • Brewer Jr., H.B.
        Familial analphalipoproteinemia: Tangier disease.
        in: Scriver C.R. Beaudet A.L. Sly E.s. Valle D. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. McGraw-Hill, New York2000: 2937-2960
        • Paryson D.
        Diagnosis of hereditary neuropathies in adult patients.
        J Neurol. 2003; 250: 148-160
        • von Eckardstein A.
        • Huang Y.
        • Kastelein J.J.P.
        • et al.
        Lipid-free apolipoprotein (apo) A-I is converted into alpha-migrating high density lipoproteins by lipoprotein depleted plasma of normolipidemic donors and apoA-I-deficient patients but not of Tangier Disease patients.
        Atherosclerosis. 1998; 138: 25-34
        • Hovingh G.K.
        • Van Wijland M.J.
        • Brownlie A.
        • et al.
        The role of the ABCA1 transporter and cholesterol efflux in familial hypoalphalipoproteinemia.
        J Lipid Res. 2003; 44: 1251-1255
        • Jonas A.
        Lecithin cholesterol acyltransferase.
        Biochim Biophys Acta. 2000; 1529: 245-256
        • Peelman F.
        • Vandekerckhove J.
        • Rosseneu M.
        Structure and function of lecithin cholesterol acyl transferase: new insights from structural predictions and animal models.
        Curr Opin Lipidol. 2000; 11: 155-160
        • Santamarina-Fojo S.
        • Hoeg J.M.
        • Assmann G.
        • Brewer Jr., H.B.
        Lecithin cholesterol acyltransferase deficiency and fish-eye disease.
        in: Scriver C.R. Beaudet A.L. Sly E.S. Valle D. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. McGraw-Hill, New York2000: 2817-2833
        • Kuivenhoven J.A.
        • Pritchard H.
        • Hill J.
        • et al.
        The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes.
        J Lipid Res. 1997; 38: 191-205
        • Kastelein J.J.
        • Pritchard P.H.
        • Erkelens D.W.
        • et al.
        Familial high-density-lipoprotein deficiency causing corneal opacities (fish eye disease) in a family of Dutch descent.
        J Intern Med. 1992; 231: 413-419
        • Calabresi L.
        • Pisciotta
        • Costantin A.
        • et al.
        The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families.
        Arteriosclerosis Throm Vasc Biol. 2005; 25: 1972-1978
        • Ayyobi A.F.
        • McGladdery S.H.
        • Chan S.
        • et al.
        Lecithin:cholesterol acyltransferase (LCAT) deficiency and risk of vascular disease: 25 year follow-up.
        Atherosclerosis. 2004; 177: 361-366
        • Zhu X.
        • Herzenberg A.M.
        • Eskandarian M.
        • et al.
        A novel in vivo lecithin-cholesterol acyltransferase (LCAT)-deficient mouse expressing predominantly LpX is associated with spontaneous glomerulopathy.
        Am J Pathol. 2004; 165: 1269-1278
        • Hovingh K.A.
        • de Groot E.
        • van der Steeg W.
        • et al.
        Inherited disorders of high density lipoprotein metabolism and atherosclerosis.
        Curr Opin Lipidol. 2005; 16: 139-145