Metabolic autopsy with next generation sequencing in sudden unexpected death in infancy: Postmortem diagnosis of fatty acid oxidation disorders.

The recent introduction of metabolic autopsy in the field of forensic science has made it possible to detect hidden inherited metabolic diseases. Since the next generation sequencing (NGS) has recently become available for use in postmortem examinations, we used NGS to perform metabolic autopsy in 15 sudden unexpected death in infancy cases. Diagnostic results revealed a case of carnitine palmitoyltransferase II deficiency and some cases of fatty acid oxidation-related gene variants. Metabolic autopsy performed with NGS is a useful method, especially when postmortem biochemical testing is not available.

Carnitine palmitoyltransferase 2 gene polymorphism is a genetic risk factor for sudden unexpected death in infancy.

RATIONALE: Carnitine palmitoyltransferase (CPT) II is one of a pivotal enzyme in mitochondrial fatty acid oxidation, which is essential for energy production during simultaneous glucose sparing and a requirement for major energy supply, such as prolonged fasting or exercise. When infants require more energy than provided by the glycolytic system, they rely on the mitochondrial fatty acid oxidation pathway. Mutations of the CPT2 gene have been reported to cause sudden unexpected death in infancy (SUDI). A thermolabile phenotype of a CPT2 polymorphism (F352C) has been recently reported to reduce CPT II enzyme activity. The F352C variant results in energy crisis at high temperature and is suspected as a risk factor for acute encephalopathy. However, a relationship between CPT2 gene polymorphism and SUDI has not been described. METHODS: Single nucleotide polymorphisms of the CPT2 gene were investigated among 54 SUDI cases and 200 healthy volunteers. RESULTS: The frequency of the C allele was significantly higher in the SUDI group than in the control group [25.0% vs 16.0%, odds ratio (OR)=1.75, 95% confidence interval (CI)=1.05-2.92, p=0.030). The frequency of the F352C homozygote was significantly higher in the SUDI group than in control group (11.1% vs 3.5%, OR=3.45, 95% CI=1.11-10.73, p=0.036). CONCLUSION: The F352C CPT2 variant might be a genetic risk factor for SUDI.

Adamantyl-functionalized polymer monolith for capillary electrochromatography.

An adamantyl (ADM)-functionalized monolithic stationary phase was newly synthesized by a single-step copolymerization of 1-adamantyl-(alpha-trifluoromethyl) acrylate, ethylene dimethacrylate, and 2-acrylamido-2-methyl-1-propanesulfonic acid in order to prevent the peak tailing of basic solutes in capillary electrochromatography and was compared with butyl methacrylate (BMA)-based one. The ADM structure shields the negatively charged groups on the surface of monolith from basic solutes, resulting in better peak shapes than BMA-based monolithic stationary phase. As the monomers ratio decreased, the monolithic column had lower retention and higher column efficiency which was likely due to lower phase ratio and smaller globule size of monolith, respectively. The ADM-functionalized monolithic columns exhibited a good repeatability and reproducibility of column preparation with relative standard deviation values below 9% in the studied chromatographic parameters.