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.
ABSTRACT
BACKGROUND: Postprandial changes in remnant-like lipoprotein particles (RLP) contribute to the severity of coronary heart disease in type 2 diabetes. Since the determinants of postprandial response in RLP are not well understood, this study investigated the roles of fasting triglyceride, apolipoprotein (apo) E polymorphism and insulin resistance in a group of overweight/obese Chinese type 2 diabetic subjects. METHODS: Postprandial triglyceride (TG) and RLP-cholesterol (RLP-C) were determined after a mixed meal containing 70-g fat at 2-h intervals for 8 h in 32 normotriglyceridemic (NTG) and 31 hypertriglyceridemic (HTG) subjects. RLP-C was measured using an immunoseparation assay and apo E genotypes using polymerase chain reaction and restriction mapping. Insulin resistance was defined as homeostasis model assessment index (HOMA-IR). RESULTS: The HTG subjects had greater postprandial increase in TG and RLP-C than NTG (p < 0.001), but there were no significant differences in HOMA-IR and apo E allele frequencies. Subjects who were non-E3-carriers had the largest postprandial increment in TG and RLP-C. On stepwise linear regression analysis, log(HOMA-IR) was only an independent determinant of fasting TG but not postprandial TG or RLP-C. The major determinants of fasting and postprandial RLP-C were fasting TG and apo E genotype, accounting for 53 and 6% of the variance of fasting RLP-C (p < 0.01) and 31 and 13% of the variance of postprandial RLP-C respectively (p < 0.01). CONCLUSIONS: Insulin resistance is mainly a determinant of fasting triglyceride in Chinese type 2 diabetic subjects, whereas apo E genotype is a better predictor of both fasting and postprandial concentrations of RLP.
