Feng Li-Fang, Chen Xiao-Hong, Li Dong-Xiao, Li Xi-Yuan, Song Jin-Qing, Jin Ying, Yang Yan-Ling
Department of Endocrinology and Metabolism, Tongji Medical College, Wuhan Children's Hospital, Huazhong University of Science and Technology, Wuhan 430015, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2018 Nov;20(11):944-949. doi: 10.7499/j.issn.1008-8830.2018.11.013.
A boy aged 6 years and 3 months developed upper respiratory tract infection and pyrexia 2 months ago and was given oral administration of nimesulide by his parents according to directions. Half an hour later, the boy experienced convulsions and cardiopulmonary arrest, and emergency examination found hypoketotic hypoglycemia, metabolic acidosis, significant increases in serum aminotransferases and creatine kinase, and renal damage. Recovery of consciousness and vital signs was achieved after cardiopulmonary resuscitation, but severe mental and movement regression was observed. The boy had a significant reduction in free carnitine in blood and significant increases in medium- and long-chain fatty acyl carnitine, urinary glutaric acid, 3-hydroxy glutaric acid, isovalerylglycine, and ethylmalonic acid, suggesting the possibility of multiple acyl-CoA dehydrogenase deficiency. After the treatment with vitamin B2, L-carnitine, and bezafibrate, the boy gradually improved, and reexamination after 3 months showed normal biochemical parameters. The boy had compound heterozygous mutations in the ETFDH gene, i.e., a known mutation, c.341G>A (p.R114H), from his mother and a novel mutation, c.1484C>G (p.P495R), from his father. Finally, he was diagnosed with multiple acyl-CoA dehydrogenase deficiency. Reye syndrome and sudden death symptoms were caused by nimesulide-induced acute metabolic crisis. It is concluded that inherited metabolic diseases may be main causes of Reye syndrome and sudden death, and biochemical and genetic analyses are the key to identifying underlying diseases.
一名6岁3个月大的男孩2个月前出现上呼吸道感染和发热,其父母按说明书给他口服了尼美舒利。半小时后,男孩出现惊厥和心肺骤停,急诊检查发现低酮性低血糖、代谢性酸中毒、血清转氨酶和肌酸激酶显著升高以及肾损伤。心肺复苏后恢复了意识和生命体征,但观察到严重的智力和运动功能倒退。男孩血液中游离肉碱显著减少,中链和长链脂肪酰肉碱、尿戊二酸、3-羟基戊二酸、异戊酰甘氨酸和乙基丙二酸显著增加,提示可能存在多种酰基辅酶A脱氢酶缺乏症。经维生素B2、L-肉碱和苯扎贝特治疗后,男孩逐渐好转,3个月后复查生化指标正常。男孩的ETFDH基因存在复合杂合突变,即来自母亲的已知突变c.341G>A(p.R114H)和来自父亲的新突变c.1484C>G(p.P495R)。最终,他被诊断为多种酰基辅酶A脱氢酶缺乏症。雷氏综合征和猝死症状是由尼美舒利诱发的急性代谢危机引起的。结论是遗传性代谢疾病可能是雷氏综合征和猝死的主要原因,生化和基因分析是识别潜在疾病的关键。