新生儿鸟氨酸氨甲酰基转移酶缺乏症

高瑞伟; 巴音; 张蓉; 曹云; 杨琳; 吴冰冰; 周文浩; 周建国

doi:10.7499/j.issn.1008-8830.2302023

PDF(1030 KB)

HTML

中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (4) : 431-435. DOI: 10.7499/j.issn.1008-8830.2302023

多学科诊疗专栏

新生儿鸟氨酸氨甲酰基转移酶缺乏症

高瑞伟¹, 巴音¹, 张蓉¹, 曹云¹, 杨琳², 吴冰冰³, 周文浩¹, 周建国¹

作者信息 +

Neonate-onset ornithine transcarbamylase deficiency

GAO Rui-Wei, BA Yin, ZHANG Rong, CAO Yun, YANG Lin, WU Bing-Bing, ZHOU Wen-Hao, ZHOU Jian-Guo

Author information +

文章历史 +

摘要

患儿男，生后15 h，因窒息复苏后呼吸困难15 h、反应差3 h入院。患儿反应极差，阵发性惊厥发作，中枢性呼吸衰竭，血氨异常增高（>1 000 μmol/L）。入院后，血串联质谱检查显示瓜氨酸明显降低，快速家系全基因组测序显示患儿为OTC基因变异，变异来自母亲。给予连续性静脉血液透析滤过等治疗，并通过脑电图和头颅磁共振检查进行神经系统评估。患儿明确诊断为鸟氨酸氨甲酰基转移酶缺乏症，合并脑损伤。生后6 d家属放弃治疗后死亡。该文对新生儿高氨血症的鉴别诊断进行重点描述，并介绍先天性遗传代谢性疾病的多学科诊疗。［中国当代儿科杂志，2023，25（4）：431-435］

Abstract

The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed OTC gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.

导出引用

高瑞伟, 巴音, 张蓉, 曹云, 杨琳, 吴冰冰, 周文浩, 周建国. 新生儿鸟氨酸氨甲酰基转移酶缺乏症[J]. 中国当代儿科杂志. 2023, 25(4): 431-435 https://doi.org/10.7499/j.issn.1008-8830.2302023

GAO Rui-Wei, BA Yin, ZHANG Rong, CAO Yun, YANG Lin, WU Bing-Bing, ZHOU Wen-Hao, ZHOU Jian-Guo. Neonate-onset ornithine transcarbamylase deficiency[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(4): 431-435 https://doi.org/10.7499/j.issn.1008-8830.2302023

参考文献

1 Matsumoto S, H?berle J, Kido J, et al. Urea cycle disorders-update[J]. J Hum Genet, 2019, 64(9): 833-847. PMID: 31110235. DOI: 10.1038/s10038-019-0614-4.
2 Donovan K, Guzman N. Ornithine transcarbamylase deficiency[M]. Treasure Island (FL): StatPearls Publishing, 2022.
3 中国妇幼保健协会儿童疾病和保健分会遗传代谢学组. 鸟氨酸氨甲酰转移酶缺乏症诊治专家共识[J]. 浙江大学学报(医学版), 2020, 49(5): 539-547. PMID: 33210478. PMCID: PMC8800749. DOI: 10.3785/j.issn.1008-9292.2020.04.11.
4 Leonard JV, Morris AA. Urea cycle disorders[J]. Semin Neonatol, 2002, 7(1): 27-35. PMID: 12069536. DOI: 10.1053/siny.2001.0085.
5 Pontoizeau C, Roda C, Arnoux JB, et al. Neonatal factors related to survival and intellectual and developmental outcome of patients with early-onset urea cycle disorders[J]. Mol Genet Metab, 2020, 130(2): 110-117. PMID: 32273051. DOI: 10.1016/j.ymgme.2020.03.003.
6 Bélanger-Quintana A, Arrieta Blanco F, Barrio-Carreras D, et al. Recommendations for the diagnosis and therapeutic management of hyperammonaemia in paediatric and adult patients[J]. Nutrients, 2022, 14(13): 2755. PMID: 35807935. PMCID: PMC9269083. DOI: 10.3390/nu14132755.
7 Wu B, Kang W, Wang Y, et al. Application of full-spectrum rapid clinical genome sequencing improves diagnostic rate and clinical outcomes in critically ill infants in the China Neonatal Genomes Project[J]. Crit Care Med, 2021, 49(10): 1674-1683. PMID: 33935161. DOI: 10.1097/CCM.0000000000005052.
8 Jezkova J, Shaw S, Taverner NV, et al. Rapid genome sequencing for pediatrics[J]. Hum Mutat, 2022, 43(11): 1507-1518. PMID: 36086948. PMCID: PMC9826377. DOI: 10.1002/humu.24466.
9 Vockley J, Aartsma-Rus A, Cohen JL, et al. Whole-genome sequencing holds the key to the success of gene-targeted therapies[J]. Am J Med Genet C Semin Med Genet, 2022. Epub ahead of print. PMID: 36453229. DOI: 10.1002/ajmg.c.32017.
10 Ozdemir Y, Cag M, Gul S, et al. In silico analysis of a de novo OTC variant as a cause of ornithine transcarbamylase deficiency[J]. Appl Immunohistochem Mol Morphol, 2022, 30(2): 153-156. PMID: 34670952. DOI: 10.1097/PAI.0000000000000979.
11 National Library of Medicine. NM_000531.6(OTC):c.275(pG>A.Arg92Gln)[EB/OL]. (2023-02-07)[2023-03-05]. https://www.ncbi.nlm.nih.gov/clinvar/variation/97152/?new_evidence=true.
12 H?berle J, Burlina A, Chakrapani A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision[J]. J Inherit Metab Dis, 2019, 42(6): 1192-1230. PMID: 30982989. DOI: 10.1002/jimd.12100.
13 Sen K, Whitehead M, Castillo Pinto C, et al. Fifteen years of urea cycle disorders brain research: looking back, looking forward[J]. Anal Biochem, 2022, 636: 114343. PMID: 34637785. PMCID: PMC8671367. DOI: 10.1016/j.ab.2021.114343.