Kento Tsuboi

Identification of malignant hyperthermia-susceptible ryanodine receptor type 1 gene (RYR1) mutations in a child who died in a car after exposure to a high environmental temperature

Malignant hyperthermia (MH) is a genetic disorder of skeletal muscle in susceptible individuals that is triggered by exposure to anesthetic agents, and can cause death. Mutations in the ryanodine receptor type 1 gene (RYR1) are associated with MH-susceptibility. MH is also triggered in susceptible individuals by severe exercise in hot conditions or by overheating in infants. Here, we report a case of a child, 2years, 9months of age, who was left in a car and exposed to a high environmental temperature. The child was suspected to have died of heat stroke by autopsy examinations. Postmortem mutation analysis revealed that the child possessed two distinct RYR1 mutations. Since each mutation had previously been identified in a separate MH-susceptible patient, MH-susceptibility with over-response to the environmental high temperature might have occurred in this child with RYR1 mutations. These findings suggest that a MH-susceptible case may have died with a presumed diagnosis of heat stroke at autopsy.

Mass spectrometric differentiation of the isomers of mono-methoxyethylamphetamines and mono-methoxydimethylamphetamines by GC–EI–MS–MS

Mass spectrometric differentiation of the six isomers of mono-methoxyethylamphetamines (MeO-EAs) and mono-methoxydimethylamphetamines (MeO-DMAs) by gas chromatography–electron ionization–tandem mass spectrometry (GC–EI–MS–MS) was investigated. Based on their EI-mass spectra, the fragment ions at m/z 121 and 72 were selected as precursor ions for their regioisomeric and structurally isomeric differentiation, respectively. Collision-induced dissociation provides intensity differences in product ions among the isomers, enabling mass spectrometric differentiation of the isomers. Furthermore, high reproducibility of the product ion spectra at the optimized collision energy was confirmed, demonstrating the reliability of the method. To our knowledge, this is the first report on mass spectrometric differentiation of the six isomers of MeO-EAs and MeO-DMAs by GC–EI–MS–MS. Isomeric differentiation by GC–EI–MS–MS has a high potential to discriminate isomers of newly encountered designer drugs, making GC–MS–MS a powerful tool in the forensic toxicology field.

Identification of a novel mutation V2321M of the cardiac ryanodine receptor gene of sudden unexplained death and a phenotypic study of the gene mutations.

Mutations of the cardiac ryanodine receptor (RyR2) gene cause catecholaminergic polymorphic ventricular tachycardia, which sometimes results in a finding of sudden unexplained death (SUD) at autopsy. We found a novel mutation (V2321M) in exon 46 of the RyR2 gene in a SUD case. V2321M was localized in a highly conservative site of the RyR2 gene, but was not found in 400 reference alleles. We previously reported two SUD cases with R420W mutations in exon 14 of the RyR2 gene. We examined possible phenotypic characteristics of all three of these cases of SUD with the RyR2 gene mutations. All cases displayed mesenteric lymph node hypertrophy as well as tendencies for aortic narrowing. By contrast, only one of the 14 SUD cases without RyR2 mutations displayed these phenotypes. This study supports the concept that postmortem genetic testing of RyR2 mutations should be considered in autopsy examinations of SUD cases. It also raises the possibility that some cases with RyR2 mutations may display phenotypic changes in lymphoid and cardiovascular organs.

Sudden death of a child because of an intestinal obstruction caused by a large congenital mesenteric defect

Transmesenteric hernias are internal hernias caused by a congenital defect in the mesentery. They are rare causes of intestinal obstruction, but most commonly affect the small bowel. We report an unexpected death of an infant with a bowel obstruction caused by a congenital mesenteric defect, which was undiagnosed despite visits to three different hospitals. Mesenteric defects are usually 2-3 cm in diameter. At autopsy, we found an oval, 14 × 7 cm congenital defect in the ileal mesentery through which the small bowel had herniated. Diagnosis of such defects remains difficult, even with currently available imaging techniques. Diagnosis is particularly difficult in infants who usually have nonspecific symptoms. Therefore, it is important that sudden unexpected deaths in children undergo full forensic evaluation to establish the precise cause of death. It is also important for forensic physicians to inform clinicians of the risk of such diseases, particularly in emergency situations.

Detection of butane gas inhalation at 16 days after hypoxic encephalopathy: A case report

In Japan, there are increasing reports of death by poisoning following butane abuse. To determine the specific cause of death in such cases, it is important to confirm the presence of fuel gas components in the body, although careful analysis is required because of their volatile properties. In most reported cases, the subject died suddenly during or immediately after butane aspiration. Thus, the butane concentration in the samples from the deceased should be relatively high. Herein, we present a case of an 18-year-old man found with cardiopulmonary arrest, who then exhibited hypoxic encephalopathy for 16days in a hospital. At autopsy, we detected hypoxic encephalopathy, pneumonia, and ischemia-reperfusion injury of the myocardium, while the cause of cardiac arrest remained unclear. Toxicological analysis was then performed for fuel gas components in several specimens collected at autopsy. Results showed that n-butane and isobutane were detected in the adipose tissue at 16days after inhalation, indicating a role of butane gas inhalation as the cause of death. These data suggest that adipose tissue may be the most appropriate analysis sample to be collected at postmortem in cases where involvement of volatile and fat-soluble gas inhalation is suspected.

Traumatic basal subarachnoid hemorrhage suspected to have been caused by contrecoup cerebellar contusions: A case report

Traumatic cerebellar hemorrhagic contusions are infrequent, and the pathogenic mechanism involves a coup injury that is associated with motor vehicle accidents in most cases. Traumatic basal subarachnoid hemorrhage (TBSAH) is commonly reported after blunt trauma to the neck or unrestricted movement of the head, and the source of the hemorrhage is most frequently identified in the vertebrobasilar arteries. A 55-year-old woman who was addicted to alcohol was found dead in her bed. She had a bruise on the left side of her posterior parietal region, and autopsy revealed massive subarachnoid hemorrhage at the base of the brain; the hematoma was strongly attached to the right lower surface of the cerebellar hemisphere. No ruptured cerebral aneurysms, arteriovenous malformations or vertebrobasilar artery leakage were detected. Hemorrhagic cerebellar contusions were regarded as the source of the TBSAH. This is the first report of TBSAH suspected to have been caused by contrecoup cerebellar contusions.