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

doi:10.7499/j.issn.1008-8830.2302023

PDF(1030 KB)

Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (4) : 431-435. DOI: 10.7499/j.issn.1008-8830.2302023

COLUMN ON DIAGNOSIS & TREATMENT IN MDT MODE

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 +

History +

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.

Key words

Ornithine transcarbamylase deficiency / Seizure / Central respiratory failure / Hyperammonemia / Neonate

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

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

References

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.