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: A C C Ho, C W Fung, T S Siu, O C K Ma, C W Lam, S Tam, V C N Wong
• Journal: JIMD reports (JIMD Rep) Vol. 12 Pg. 129-34 ( 2014) ISSN: 2192-8304 [Print] United States
• PMID: 24142275 (Publication Type: Journal Article)