精氨酰琥珀酸尿症致反复高氨血症1例报告
|
摘要
目的探讨精氨酰琥珀酸尿症致反复高氨血症的诊断和治疗。方法回顾分析1例精氨酰琥珀酸尿症患儿的诊治及随访经过,并复习相关文献。结果患儿,男,13个月,因呕吐、嗜睡、反应差入院,检查发现血氨升高(138.02μmol/L),肝功能异常,伴低钾血症,血瓜氨酸升高(65.64μmol/L);脑电图异常。完善高氨血症相关基因的二代基因测序,发现精氨酰琥珀酸裂解酶基因(ASL)复合杂合突变。予以限制蛋白饮食、补充精氨酸治疗,患儿高氨血症仍反复发作,肝脏进行性增大;确诊1年后行肝移植。移植后1年,患儿肝功能、血氨无异常,生长发育无异常。结论精氨酰琥珀酸尿症临床表现复杂,高氨血症是其重要表现;基因检查有助确诊,肝移植治疗有效。
Objective To explore the diagnosis and treatment of recurrent hyperammonemia caused by argininosuccinic aciduria. Method The diagnosis, treatment and follow-up of argininosuccinic aciduria in a child were retrospectively analyzed,and the related literature was reviewed. Results A 13-month-old boy was admitted to hospital for vomiting, sleepiness and poor reaction. The results showed elevated blood ammonia( 138. 02 μmol/L), abnormal liver function, hypokalemia, elevated blood citrulline( 65. 64 Umol/L), and abnormal electroencephalogram. The second generation gene sequencing was performed on hyperammonia-related genes, and the compound heterozygous mutation of argininosuccinate lyase(ASL) gene was found.After the treatment with protein restriction diet and arginine supplementation, the children's hyperammonia still recurred and the liver was progressively enlarged. One year after the diagnosis, liver transplantation was performed. At present, 1 year after transplantation, the liver function, blood ammonia, growth and development of the child were normal. Conclusion The clinical manifestations of argininosuccinic aciduria are complex, and hyperammonia is an important manifestation. Gene examination is helpful for diagnosis and liver transplantation is effective.
Objective To explore the diagnosis and treatment of recurrent hyperammonemia caused by argininosuccinic aciduria. Method The diagnosis, treatment and follow-up of argininosuccinic aciduria in a child were retrospectively analyzed,and the related literature was reviewed. Results A 13-month-old boy was admitted to hospital for vomiting, sleepiness and poor reaction. The results showed elevated blood ammonia( 138. 02 μmol/L), abnormal liver function, hypokalemia, elevated blood citrulline( 65. 64 Umol/L), and abnormal electroencephalogram. The second generation gene sequencing was performed on hyperammonia-related genes, and the compound heterozygous mutation of argininosuccinate lyase(ASL) gene was found.After the treatment with protein restriction diet and arginine supplementation, the children's hyperammonia still recurred and the liver was progressively enlarged. One year after the diagnosis, liver transplantation was performed. At present, 1 year after transplantation, the liver function, blood ammonia, growth and development of the child were normal. Conclusion The clinical manifestations of argininosuccinic aciduria are complex, and hyperammonia is an important manifestation. Gene examination is helpful for diagnosis and liver transplantation is effective.
引文
[1]Tuchman M,Lee B,Lichter-Konecki U,et al.Cross-sectional multicenter study of patients with urea cycle disorders in the United States[J].Mol Genet Metab,2008,94(4):397-402.
[2]丁圆,马艳艳,吴桐菲,等.精氨酰琥珀酸尿症导致新生儿死亡1例报告[J].临床儿科杂志,2014,32(12):1112-1115.
[3]AlTassan R,Bubshait D,Imtiaz,et al.A retrospective biochemical,molecular,and neurocognitive review of Saudi patients with argininosuccinic aciduria[J].Eur J Med Genet,2018,61(6):307-311.
[4]Ah Mew N,Krivitzky L,McCarter R,et al.Clinical outcomes of neonatal onset proximal versus distal urea cycle disorders do not differ[J].J Pediatr,2013,162(2):324-329.
[5]Fichtel JC,Richards JA,Davis LS.Trichorrhexis nodosa secondary to argininosuccinicaciduria[J].Pediatr Dermatol,2007,24(1):25-27.
[6]Mori T,Nagai K,Mori M,et al.Progressive liver fibrosis in late-onset argininosuccinate lyasedeficiency[J].Pediatr Dev Pathol,2002,5(6):597-601.
[7]Widhalm K,Koch S,Scheibenreiter S,et al.Long-term follow-up of 12 patients with the late-onset variant of argininosuccinic acid lyase deficiency:no impairment of intellectual and psychomotor development during therapy[J].Pediatrics,1992,89(6 Pt 2):1182-1184.
[8]Nagamani SC,Erez A,Lee B.Argininosuccinate lyase deficiency[J].Genet Med,2012,14(5):501-507.
[9]林壹明,余科,李鹿丰,等.六例瓜氨酸血症患儿的ASS1、ASL和SLC25A13基因突变分析[J].中华医学遗传学杂志,2017,34(5):676-679.
[10]Balmer C,Pandey AV,Rüfenacht V,et al.Mutations and polymorphisms in the human argininosuccinate lyase(ASL)gene[J].Hum Mutat,2014,35(1):27-35.
[11]Baruteau J,Jameson E,Morris AA,et al.Expanding the phenotype in argininosuccinic aciduria:need for new therapies[J].J Inherit Metab Dis,2017,40(3):357-368.
[12]Premkumar MH,Sule G,Nagamani SC,et al.Argininosuccinate lyase in enterocytes protects from development of necrotizing enterocolitis[J].Am J Physiol Gastrointest Liver Physiol,2014,307(3):G347-G354.
[13]Erez A,Nagamani SC,Lee B.Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond[J].Am JMed Genet C Semin Med Genet,2011,157(1):45-53.
[14]Yankol Y,Mecit N,Kanmaz T,et al.Argininosuccinic aciduria-a rare indication for liver transplant:report of two cases[J].Exp Clin Transplant,2017,15(5):581-584.
[15]H?berle J,Koch HG.Genetic approach to prenatal diagnosis in urea cycle defects[J].Prenat Diagn,2004,24(5):378-383.
[2]丁圆,马艳艳,吴桐菲,等.精氨酰琥珀酸尿症导致新生儿死亡1例报告[J].临床儿科杂志,2014,32(12):1112-1115.
[3]AlTassan R,Bubshait D,Imtiaz,et al.A retrospective biochemical,molecular,and neurocognitive review of Saudi patients with argininosuccinic aciduria[J].Eur J Med Genet,2018,61(6):307-311.
[4]Ah Mew N,Krivitzky L,McCarter R,et al.Clinical outcomes of neonatal onset proximal versus distal urea cycle disorders do not differ[J].J Pediatr,2013,162(2):324-329.
[5]Fichtel JC,Richards JA,Davis LS.Trichorrhexis nodosa secondary to argininosuccinicaciduria[J].Pediatr Dermatol,2007,24(1):25-27.
[6]Mori T,Nagai K,Mori M,et al.Progressive liver fibrosis in late-onset argininosuccinate lyasedeficiency[J].Pediatr Dev Pathol,2002,5(6):597-601.
[7]Widhalm K,Koch S,Scheibenreiter S,et al.Long-term follow-up of 12 patients with the late-onset variant of argininosuccinic acid lyase deficiency:no impairment of intellectual and psychomotor development during therapy[J].Pediatrics,1992,89(6 Pt 2):1182-1184.
[8]Nagamani SC,Erez A,Lee B.Argininosuccinate lyase deficiency[J].Genet Med,2012,14(5):501-507.
[9]林壹明,余科,李鹿丰,等.六例瓜氨酸血症患儿的ASS1、ASL和SLC25A13基因突变分析[J].中华医学遗传学杂志,2017,34(5):676-679.
[10]Balmer C,Pandey AV,Rüfenacht V,et al.Mutations and polymorphisms in the human argininosuccinate lyase(ASL)gene[J].Hum Mutat,2014,35(1):27-35.
[11]Baruteau J,Jameson E,Morris AA,et al.Expanding the phenotype in argininosuccinic aciduria:need for new therapies[J].J Inherit Metab Dis,2017,40(3):357-368.
[12]Premkumar MH,Sule G,Nagamani SC,et al.Argininosuccinate lyase in enterocytes protects from development of necrotizing enterocolitis[J].Am J Physiol Gastrointest Liver Physiol,2014,307(3):G347-G354.
[13]Erez A,Nagamani SC,Lee B.Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond[J].Am JMed Genet C Semin Med Genet,2011,157(1):45-53.
[14]Yankol Y,Mecit N,Kanmaz T,et al.Argininosuccinic aciduria-a rare indication for liver transplant:report of two cases[J].Exp Clin Transplant,2017,15(5):581-584.
[15]H?berle J,Koch HG.Genetic approach to prenatal diagnosis in urea cycle defects[J].Prenat Diagn,2004,24(5):378-383.