Genetic analysis of ryanodine receptor 1 gene and carnitine palmitoyltransferase II gene: an autopsy case of neuroleptic malignant syndrome related to vegetamin.

Abstract We report an autopsy case of a man in his forties who died 2days after taking an overdose of vegetamin. The autopsy findings were as follows: externally, the upper epidermis of some parts of the body had become loosened. The epidermis was easily detached from the dermis using the fingers. Viscous fluid adhered around the nose and mouth. The brain was edematous and weighed 1520g. Skeletal muscle was discolored. The urine was a slightly red-tinged yellow. The organs showed congestion. Urine tests: urea nitrogen: 1.95g/day; creatinine: 0.66g/day; urine myoglobin: 1100ng/mL. Blood level of drugs: phenobarbital: 38.2μg/ml; promethazine: 2.22μg/ml; chlorpromazine: 0.96μg/ml. Immunohistochemistry identified myoglobin in the kidney. From these findings, his cause of death was considered to be vegetamin-induced neuroleptic malignant syndrome and rhabdomyolysis. Mutation of the ryanodine receptor 1 gene is associated with malignant hyperthermia. However, there was no mutation which causes amino acid substitution in the three hot-spot regions of the ryanodine receptor 1 gene. Partial deficiency of carnitine palmitoyltransferase II is the commonest cause of recurrent rhabdomyolysis in adults. The subject was found to be heterozygous for an amino acid exchange in exon 4, 1203 G→A causing a 368 Val→Ile amino acid substitution. It is necessary to examine other candidate gene mutations.