Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review

BMC Medical Genomics

Case Report

Hao Qian¹  Haifeng Xu¹  Haiying Lu¹  Hu Guo¹  Gang Zhang¹  Wenxin Lin¹  Shangyu Wang¹  Guo Zheng¹  Kaleem Ullah Khan¹  Tingting Huang¹  Guohuan Ying¹  Yiehen Tung¹  Xiaoqi Zhu²  Jinglin Chen² 

[1]Department of Neurology, Children’s Hospital of Nanjing Medical University, No.72 Guangzhou Road, Nanjing, Jiangsu, China

[2]Nanjing Medical University, Nanjing, China

关键词: Hyperammonemia;    CPS1;    Emerging mutations;    Urea cycle disorder/carbamoyl phosphate synthase I deficiency;   

DOI  :  10.1186/s12920-023-01569-w

 received in 2022-09-18, accepted in 2023-06-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCarbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1.Case presentationWe present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis.ConclusionA comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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