Genetic analysis of rhab domyolysis-associated genes: an autopsy case of metham phetam ine-related hyperthermia and acidosis

Abstract

In an autopsy case of methamphetamine (MA)-related hyperthermia and acidosis, we investigated the genetic background of hyperthermia and muscular hyperactivity in relation to rhabdomyolysis. We examined mutations in the ryanodine receptor1 (RYR1) gene, which is associated with malignant hyperthermia, the very long-chain acyl-CoA dehydrogenase (VLCAD) gene, which is associated with rhabdomyolysis, the carnitine palmitoyltransferase II (CPT II) gene, which is the most common cause of recurrent rhabdomyolysis in adults and the cytochrome P450 (CYP)2D6 gene which encodes MA-metabolizing enzyme. There were two homozygous and three heterozygous silent mutations in the three hot-spot regions in the RYR1 gene. There was no mutation in the VLCAD gene. In the CPT II gene, the subject was found to be homozygous for two amino acid substitutions, 352Phe>Cys and 368Val>Ile in exon 4. In the CYP2D6 gene, the subject was heterozygous for 100C>T, 1661G>C and 4180G>C causing 34Pro>Ser, a silent mutation and 486Ser>Thr, respectively, in the CYP2D6*10A allele