title: Lathosterolosis: a disorder of cholesterol biosynthesis resembling smith-lemli-opitz syndrome.
abstract: Lathosterolosis is an inborn error of cholesterol biosynthesis due to deficiency of the enzyme 3-beta-hydroxysteroid-delta-5-desaturase (or sterol-C5-desaturase or SC5D). This leads to a block in conversion of lathosterol into 7-dehydrocholesterol. Only three patients with lathosterolosis have been reported in literature, of which one survived. We report a patient with dysmorphism, multiple congenital anomalies, and developmental delay, initially suspected to have Smith-Lemli-Opitz syndrome, who was later found to have elevated levels of lathosterol in both plasma and fibroblasts. Genetic study confirmed a compound heterozygous mutation in the sterol-C5-desaturase-like (SC5DL) gene on chromosome 11q23. Simvastatin was started as a treatment therapy and it resulted in normalization of blood lathosterol level and improvement in the neurodevelopmental profile. However, additional patients are needed for better delineation of the clinical spectrum, genotype-phenotype correlation, and potential efficacy of simvastatin treatment in this rare disorder. If the presence of distinctive facial features and limb anomalies raise the suspicion of a cholesterol biosynthesis defect, testing of full sterol profile is warranted as normal cholesterol or 7-dehydrocholesterol levels cannot rule out the diagnosis of cholesterol synthesis defect like lathosterolosis.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: A C C
authors.initials: AC
authors.lastname: Ho
authors.forename: C W
authors.initials: CW
authors.lastname: Fung
authors.forename: T S
authors.initials: TS
authors.lastname: Siu
authors.forename: O C K
authors.initials: OC
authors.lastname: Ma
authors.forename: C W
authors.initials: CW
authors.lastname: Lam
authors.forename: S
authors.initials: S
authors.lastname: Tam
authors.forename: V C N
authors.initials: VC
authors.lastname: Wong