苯丁酸甘油酯治疗精氨酰琥珀酸合成酶缺乏症1例

Glyceryl phenylbutyrate in the treatment of argininosuccinate synthetase deficiency: a case report

回顾性分析湖南省儿童医院1例血氨高疑诊为精氨酰琥珀酸合成酶缺乏症(ASSD)患儿资料,患儿行血液氨基酸及酰基肉碱谱分析、尿有机酸分析、全外显子测序等检查,确诊后至海南博鳌医疗先行区通过"海南临床急需进口药物申报"管控用药途径接受苯丁酸甘油酯(GPB)治疗并随访。患儿,男,7岁8个月,因"嗜睡、精神行为异常、性格改变1周"于2021年12月2日在湖南省儿童医院神经内科就诊。血氨最高325.2μmol/L,丙氨酸转氨酶465.7 IU/L,天冬氨酸转氨酶277.3 IU/L,血尿遗传代谢示瓜氨酸明显升高(697.42μmol/L);尿有机酸分析示尿乳清酸水平升高(144.2μmol/L)、尿嘧啶水平升高(65.1μmol/L);基因报告仅发现ASS1基因单纯杂合变异(c.1087C>T,p.R363W)。治疗后随访第41天、第90天和第146天血氨分别为21.3μmol/L、54.6μmol/L和62.4μmol/L。随访至2022年7月20日,效果好,未见任何不良反应。本病例为中国首例接受GPB治疗的ASSD患儿,丰富了中国治疗ASSD的经验谱。ASSD病死率高,不明原因精神行为异常,需完善血氨检查警惕尿素循环障碍系列疾病,该病诊断和管理应参考代谢异常和基因检查共同进行。

Clinical data of a child with high blood ammonia and suspected argininosuccinate synthetase deficiency(ASSD)in Hunan Children′s Hospital were retrospectively analyzed,including data of mass spectra for blood amino acids and acyl carnitine,urine organic acid analysis and whole exome sequencing.After the exact diagnosis of ASSD and being approved by the Administrative Regulation for Import Medical Devices Urgently Needed in Boao Lecheng International Medical Tourism Pilot Zone of Hainan Free Trade Port,the patient was medicated with Glyceryl phenylbutyrate(GPB)and followed up.The patient was a boy aged 7 years and 8 months,who presented at the Neurology Department of Hunan Children′s Hospital for sleepiness,abnormal mental behavior and personality change for 1 week on December 2,2021.Before GPB treatment,the highest blood ammonia,alanine aminotransferase and aspartate transaminase were 325.2μmol/L,465.7 IU/L and 277.3 IU/L,respectively.Genetic metabolism assay of blood and urine showed a significantly increased citrulline at 697.42μmol/L;urine organic acid analysis showed increased urinary orotic acid at 144.2μmol/L,and increased uracil at 65.1μmol/L.A pure heterozygous variant of the ASS1 gene(c.1087C>T,p.R363W)was detected.After GPB treatment,the blood ammonia levels were 21.3μmol/L,54.6μmol/L and 62.4μmol/L on the 41st,90th and 146th days,respectively.Until July 20,2022 follow-up visit,the patient recovered well without adverse events.This was the first ASSD child in China who was treated with GPB.This case report provided therapeutic experience of ASSD in our country.ASSD has a high mortality rate and unexplained abnormal mental behavior.It is necessary to timely measure blood ammonia,and a series of urea cycle disorders should be well concerned.The diagnosis and management of ASSD rely on the data of metabolism examination and genetic testing.