title: Proteinuria in early childhood due to familial LCAT deficiency caused by loss of a disulfide bond in lecithin:cholesterol acyl transferase.
abstract: BACKGROUND
  Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare recessive disorder of cholesterol metabolism characterized by the absence of high density lipoprotein (HDL) and the triad of corneal opacification, hemolytic anemia and glomerulopathy.
  
  
  METHODS
  We here report on FLD in three siblings of a kindred of Moroccan descent with HDL deficiency. In all cases (17, 12 and 3 years of age) corneal opacification and proteinuria were observed. In the 17-year-old female proband, anemia with target cells was observed.
  
  
  RESULTS
  Homozygosity for a mutation in LCAT resulted in the exchange of cysteine to tyrosine at position 337, disrupting the second disulfide bond in LCAT. LCAT protein and activity were undetectable in the patients' plasma and in media of COS7 cells transfected with an expression vector with mutant LCAT cDNA. Upon treatment with an ACE inhibitor and a thiazide diuretic, proteinuria in the proband decreased from 6g to 2g/24h.
  
  
  CONCLUSIONS
  This is the first report that FLD can cause nephropathy at a very early age.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. a.g.holleboom@amc.uva.nl
authors.forename: A G
authors.initials: AG
authors.lastname: Holleboom
authors.forename: J A
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: C C
authors.initials: CC
authors.lastname: van Olden
authors.forename: J
authors.initials: J
authors.lastname: Peter
authors.forename: A W
authors.initials: AW
authors.lastname: Schimmel
authors.forename: J H
authors.initials: JH
authors.lastname: Levels
authors.forename: R M
authors.initials: RM
authors.lastname: Valentijn
authors.forename: P
authors.initials: P
authors.lastname: Vos
authors.forename: J C
authors.initials: JC
authors.lastname: Defesche
authors.forename: J J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: G K
authors.initials: GK
authors.lastname: Hovingh
authors.forename: E S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: C E M
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D000293:Adolescent; D000743:Anemia, Hemolytic / Q000201:enzymology / Q000235:genetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D008076:Cholesterol, HDL / Q000097:blood; D003318:Corneal Opacity / Q000201:enzymology / Q000235:genetics; D003545:Cysteine; D004220:Disulfides / Q000737:chemistry*; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D014162:Transfection; D016896:Treatment Outcome; D014443:Tyrosine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008076:Cholesterol, HDL; D004220:Disulfides; D004232:Diuretics; D014443:Tyrosine; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D003545:Cysteine