1. Clinical features and CPS1 variants in Chinese patients with carbamoyl phosphate synthetase 1 deficiency.
- Author
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Dong H, Sang T, Ma X, Song J, Chen Z, Zhang H, Jin Y, Li M, Dong D, Sun L, Zhu Z, Zhang Y, and Yang Y
- Subjects
- Humans, Female, Male, Infant, Child, Child, Preschool, Adolescent, Infant, Newborn, China, Mutation, Young Adult, Asian People genetics, East Asian People, Carbamoyl-Phosphate Synthase I Deficiency Disease genetics, Carbamoyl-Phosphate Synthase (Ammonia) genetics
- Abstract
Background: Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality., Methods: Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children's Medical Center of Peking University First Hospital from September 2014 to August 2023., Results: Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506_3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing., Conclusions: Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1., (© 2024. The Author(s).)
- Published
- 2024
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