title: Clinical phenotype of desmosterolosis.
abstract: We describe a child with lethal multiple malformations and generalised accumulation of desmosterol. The infant had macrocephaly, a hypoplastic nasal bridge, thick alveolar ridges, gingival nodules, cleft palate, total anomalous pulmonary venous drainage, ambiguous genitalia, short limbs, and generalised osteosclerosis. Gas chromatography-mass spectrometry demonstrated an abnormal accumulation of desmosterol in kidney, liver. and brain. Higher than normal levels of the same sterol were detected in plasma samples obtained from both parents. The biochemical phenotype in this infant is highly suggestive of a novel inborn error of cholesterol biosynthesis caused by an autosomal recessive deficiency of 3betahydroxysterol-delta24-reductase. A phenotypic overlap of this case with Raine syndrome was noted; however, desmosterol accumulation was not found on postmortem tissue samples from a previously reported case of this disorder.
authors.affiliation: Department of Clinical Genetics, Molecular Medicine Centre, WGH, Edinburgh, Scotland, United Kingdom. david.fitzpatrick@ed.ac.uk
authors.forename: D R
authors.initials: DR
authors.lastname: FitzPatrick
authors.forename: J W
authors.initials: JW
authors.lastname: Keeling
authors.forename: M J
authors.initials: MJ
authors.lastname: Evans
authors.forename: A E
authors.initials: AE
authors.lastname: Kan
authors.forename: J E
authors.initials: JE
authors.lastname: Bell
authors.forename: M E
authors.initials: ME
authors.lastname: Porteous
authors.forename: K
authors.initials: K
authors.lastname: Mills
authors.forename: R M
authors.initials: RM
authors.lastname: Winter
authors.forename: P T
authors.initials: PT
authors.lastname: Clayton
mesh_terms: D000015:Abnormalities, Multiple / Q000473:pathology*; D000328:Adult; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood; D003897:Desmosterol / Q000097:blood*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013577:Syndrome; D014018:Tissue Distribution
chemical_list: D003897:Desmosterol; D002784:Cholesterol