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

Abstract

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 3.45, 95% CI = 1.11-10.73, p = 0.036). Conclusion: The F352C CPT2 variant might be a genetic risk factor for SUDI.

Heat stroke with bimodal rhabdomyolysis: a case report and review of the literature

“…CPT II is 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 during prolonged fasting or exercise [31]. Cases with the thermolabile genetic phenotype of CPT II have been described mainly in Japan and China.…”

“…Cases with the thermolabile genetic phenotype of CPT II have been described mainly in Japan and China. Recent studies have suggested the association of this phenotype with influenza-associated encephalopathy, encephalopathy during a high-grade fever caused by human herpesvirus-6, enterovirus 71, Echo virus, Coxsackievirus, rotavirus, respiratory syncytial virus, adenovirus infection, or sudden unexpected death in infancy [31–40]. Generally, CPT II deficiency has three clinical presentations: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form (which is usually mild and can manifest from infancy to adulthood) [41].…”

No association between cardiac ion channel variants and sudden infant death

“…Serotonin transporter polymorphism was first reported by Narita et al 3 We also reported that the carnitine palmitoyltransferase2 variant is a risk factor. 4 Other than these, there are variants of arrhythmia channel genes, which are detected in healthy controls and which affect the cardiac ion channel currents. There are no studies, however, on the genetic frequencies of these arrhythmia channel gene variants, and it is controversial as to whether these variants are associated with SUD in infancy.…”

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

“…Since these two substitutions are common genetic polymorphisms [18], [19], [20], [21], [22], they were excluded from the targeted NGS analysis.…”