title: A kindred with fish eye disease, corneal opacities, marked high-density lipoprotein deficiency, and statin therapy.
abstract: A kindred affected with fish eye disease (FED) from Oklahoma is reported. Two probands with corneal opacification had mean levels of high-density lipoprotein (HDL) cholesterol (C), apolipoprotein (apo) A-I, and apoA-I in very large alpha-1 HDL particles that were 9%, 17%, and 5% of normal, whereas their parents and 1 sibling had values that were 61%, 77%, and 72% of normal. The probands had no detectable lipoprotein-X, and had mean low-density lipoprotein cholesterol (LDL-C) and triglyceride levels that were elevated. Their mean lecithin cholesterol acyltransferase (LCAT) activities, cholesterol esterification rates, and free cholesterol levels were 8%, 42%, and 258% of normal, whereas their parents and 1 sibling had values that were 55%, 49%, and 114% of normal. The defect was due to 1 common variant in the LCAT gene in exon 1: c101t causing a proline34leucine substitution and a novel mutation c1177t causing a threonine37methionine substitution, with the former variant being found in the father and 1 sibling, and the latter mutation being found in the mother, and both mutations being present in the 2 probands. FED is distinguished from familial LCAT deficiency (FLD) by the lack of anemia, splenomegaly, and renal insufficiency as well as normal or increased LDL-C. Both FLD and FED cases have marked HDL deficiency and corneal opacification, and FED cases may have premature coronary heart disease in contrast to FLD cases. Therapy, using presently available agents, in FED should be to optimize LDL-C levels, and 1 proband responded well to statin therapy. The investigational use of human recombinant LCAT as an enzyme source is ongoing.
authors.affiliation: Central Oklahoma Early Detection Center, Lipidology and Cardiometabolic Clinic, 1227 East 9th Street, Edmond, OK 73034, USA; The University of Oklahoma College of Medicine, 941 Stanton L. Young Boulevard, Oklahoma City, Oklahoma 73104, USA. Electronic address: susandimickmd@hotmail.com.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Dimick
authors.affiliation: Central Oklahoma Early Detection Center, Lipidology and Cardiometabolic Clinic, 1227 East 9th Street, Edmond, OK 73034, USA; The University of Oklahoma College of Medicine, 941 Stanton L. Young Boulevard, Oklahoma City, Oklahoma 73104, USA. Electronic address: brigitte-sallee@ouhsc.edu.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sallee
authors.affiliation: Boston Heart Diagnostics, Framingham, MA, USA; Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.affiliation: Atherosclerosis Specialty Laboratory, Department of Pathology and Laboratory Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: P Haydn
authors.initials: PH
authors.lastname: Pritchard
authors.affiliation: Atherosclerosis Specialty Laboratory, Department of Pathology and Laboratory Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Jiri
authors.initials: J
authors.lastname: Frohlich
authors.affiliation: Boston Heart Diagnostics, Framingham, MA, USA; Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
mesh_terms: D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003318:Corneal Opacity / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: Alpha-1 HDL; ApoA-I; Atherosclerosis; Cholesterol esterification; Familial LCAT deficiency; Fish eye disease; HDL Map; LCAT; Renal function; Statin