title: Clinical phenotype of lathosterolosis.
abstract: Lathosterolosis (LS) is a defect of cholesterol biosynthesis due to the deficiency of the enzyme sterol-C5-desaturase. Only two patients have been described to date, both presenting with multiple malformations, mental retardation, and liver involvement. In addition in one of them pathological examination revealed mucolipidosis-like inclusions on optic microscopy analysis, and peculiar lysosomal lamellar bodies on electron microscopy analysis. This study is focused on a better characterization of the clinical phenotype of LS. We describe a further case in a fetus, sibling of the first patient reported, presenting with neural tube defect, craniofacial and limb anomalies, and prenatal liver involvement. The fetal phenotype suggests the possible occurrence of significant intrafamilial variability in LS, and expands the phenotypic spectrum of the disease. Histological examination of autopsy samples from the fetus and skin fibroblasts from the living sibling suggested that the mucolipidosis-like picture previously reported is not a constant feature of LS, being possibly associated with the most severe biochemical defects, but confirmed the ultrastructural finding of lamellar inclusions. The LS phenotype appears to be characterized by the distinctive association of a recognizable pattern of congenital anomalies, involving axial and appendicular skeleton, liver, central nervous and urogenital systems, and lysosomal storage. This condition partially overlaps with other defects of sterol metabolism, suggesting intriguing pathogenic links among these conditions.
authors.affiliation: Dipartimento di Pediatria, Federico II University, Naples, Italy, and Department of Radiology, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Rossi
authors.forename: Maria
authors.initials: M
authors.lastname: D'Armiento
authors.forename: Ida
authors.initials: I
authors.lastname: Parisi
authors.forename: Paola
authors.initials: P
authors.lastname: Ferrari
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hall
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Cervasio
authors.forename: Francesco
authors.initials: F
authors.lastname: Rivasi
authors.forename: Fiorella
authors.initials: F
authors.lastname: Balli
authors.forename: Raffaella
authors.initials: R
authors.lastname: Vecchione
authors.forename: Gaetano
authors.initials: G
authors.lastname: Corso
authors.forename: Generoso
authors.initials: G
authors.lastname: Andria
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
mesh_terms: D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism*; D000013:Congenital Abnormalities / Q000473:pathology; D005260:Female; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology*; D008297:Male; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency / Q000378:metabolism; D010641:Phenotype; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics / Q000473:pathology
chemical_list: C033144:lathosterol delta-5-dehydrogenase; C001521:lathosterol; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors