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

• Published in: Legal medicine (Tokyo, Japan) Vol. 11; pp. S570 - S572
• Main Authors: Matsusue, Aya, Hara, Kenji, Kageura, Mitsuyoshi, Kashiwagi, Masayuki, Lu, Wang, Ishigami, Akiko, Gotohda, Takako, Tokunaga, Itsuo, Nisimura, Akiyoshi, Sugimura, Tomoko, Kubo, Shin-ichi
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.04.2009
• Subjects: Adult; Amino Acid Substitution; Antipsychotic Agents - poisoning; Brain - pathology; Brain Edema - pathology; Carnitine O-Palmitoyltransferase - genetics; Carnitine palmitoyltransferase II; Chlorpromazine - poisoning; Creatinine - urine; Drug Combinations; Drug Overdose; Epidermis - pathology; Exons; Forensic Genetics; Forensic Pathology; Heterozygote; Humans; Internal Medicine; Kidney - pathology; Male; Muscle, Skeletal - pathology; Myoglobinuria - etiology; Neuroleptic Malignant Syndrome - etiology; Nitrogen - urine; Organ Size; Phenobarbital - poisoning; Rhabdomyolysis; Rhabdomyolysis - chemically induced; Rhabdomyolysis - diagnosis; Ryanodine receptor 1; Ryanodine Receptor Calcium Release Channel - genetics; Suicide; Urea - urine; Carnitine palmitoyltransferase II; Ryanodine receptor 1; Rhabdomyolysis
• ISSN: 1344-6223; 1873-4162
• DOI: 10.1016/j.legalmed.2009.01.074

Abstract We report an autopsy case of a man in his forties who died 2 days 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 1520 g. Skeletal muscle was discolored. The urine was a slightly red-tinged yellow. The organs showed congestion. Urine tests: urea nitrogen: 1.95 g/day; creatinine: 0.66 g/day; urine myoglobin: 1100 ng/mL. Blood level of drugs: phenobarbital: 38.2 μg/ml; promethazine: 2.22 μg/ml; chlorpromazine: 0.96 μg/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 a368 Val → Ile amino acid substitution. It is necessary to examine other candidate gene mutations.