However, in infantile onset patients, the clinical manifestations are somehow similar among all types of lipid dysmetabolism, including hypotonia, hypoketotic hypoglycemic encephalopathy, hepatomegaly and cardiomyopathy. In this review, we would like to go through CPTII and VLCAD deficiencies briefly but mainly focus on four LSMs with known causative genes, PCD, MADD, NLSDI and NLSDM. Inhibitors,research,lifescience,medical Carnitine palmitoyltransferase

II deficiency (CPTII deficiency) CPTII, located at the inner mitochondrial membrane, is responsible for the transfer of long-chain acyl-CoA (Fig. 1), thus the defects in CPTII would apparently affect the access of long-chain acyl-CoA to β-oxidation. CPTII deficiency caused

by the mutations Inhibitors,research,lifescience,medical in the CPT2 gene is the first inherited defect of fatty acid oxidation to be identified (2). Three clinical subtypes, neonatal, infantile and mild late-onset forms, have been described but muscular symptoms including recurrent rhabdomyolysis and muscle pain after long-term exercise were mainly associated with the late-onset form (3). Infantile cases usually present recurrent attacks of acute liver failure with hypoketotic hypoglycemia, cardiomyopathy and sudden Inhibitors,research,lifescience,medical death while neonatal-onset patients demonstrate a more severe phenotype with dysmorphic features. There is a good correlation between genotype, metabolic dysfunction and phenotype as null or truncated mutations often cause absent enzyme activity and earlier-onset phenotype (2). A common mutation, p.S113L, has been found in more than 50% of Inhibitors,research,lifescience,medical mutant alleles in mild late-onset patients. Figure 1. Scheme of selected metabolic pathways of lipid. (OCTN2: plasma membrane sodium-dependent Inhibitors,research,lifescience,medical carnitine transporter; TG: triglycerides; DG: diglycerides; ATGL: adipose triglyceride lipase; CGI-58: comparative

gene identification-58; CPTI: carnitine palmitoyltransferase I; … Metabolic profiles in CPTII deficiency patients usually show increased long-chain acylcarnitines. Creatine kinase (CK) level is markedly elevated after prolonged fasting or exercise. Muscle pathology is typically characterized by Selleck PF-477736 nonspecific secondly changes without increased lipid droplets. Therefore, enzymatic assay in leukocyte, cultured fibroblasts or biopsied muscles may be the most reliable diagnostic test, as well as the mutation analysis for CPT2. The treatment for CPTII deficiency is mainly dependent on restricting the diet and avoiding fasting. Long-chain fat –restricted diet with medium-chain triglycerides (MCT) supplementation is recommended (4). Recently, bezafibrate, a commonly used hypolipidemic drug, has shown to restore the capacity for normal fatty acid oxidation in muscle cells from patients with a mild form of CPTII deficiency (5).