Variant in the allosteric domain of CPS1 protein associated with effectiveness of N-carbamoyl glutamate therapy in neonatal onset CPS1 deficiency.
J Pediatr Endocrinol Metab
; 36(9): 873-878, 2023 Sep 26.
Article
em En
| MEDLINE
| ID: mdl-37427576
ABSTRACT
OBJECTIVES:
Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a severe urea cycle disorder. Patients can present with hyperammonemic coma in the first days of life. Treatment includes nitrogen scavengers, reduced protein intake and supplementation with L-arginine and/or L-citrulline. N-carbamoyl glutamate (NCG) has been hypothesized to stimulate the residual CPS1 function, although only few patients are reported. CASE PRESENTATION We report a patient with neonatal-onset CPS1 deficiency who received NCG in association with nitrogen scavenger and L-citrulline. The patient carried the novel variants CPS1-c.2447A>G p.(Gln816Arg) and CPS1-c.4489T>C p.(Tyr1497His). The latter is localized in the C-terminal allosteric domain of the protein, and is implicated in the binding of the natural activator N-acetyl-L-glutamate. NCG therapy was effective in controlling ammonia levels, allowing to increase the protein intake.CONCLUSIONS:
Our data show that the response to NCG can be indicated based on the protein structure. We hypothesize that variants in the C-terminal domain may be responsive to NCG therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença da Deficiência da Carbamoil-Fosfato Sintase I
/
Distúrbios Congênitos do Ciclo da Ureia
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
/
Newborn
Idioma:
En
Revista:
J Pediatr Endocrinol Metab
Assunto da revista:
ENDOCRINOLOGIA
/
PEDIATRIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Itália