Dados do Trabalho

Título

INFANT WITH ATYPICAL PRESENTATION OF ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY

Apresentação do caso único

A 17-month-old female patient presented with vomiting associated with altered consciousness and seizure, accompanied by fever. Initial diagnostic suspicion was meningoencephalitis; however, cerebrospinal fluid (CSF) was negative and the case was managed as viral encephalitis. Persistent cerebral edema with signs of intracranial hypertension was observed, partially responding to therapeutic measures, necessitating a ventriculoperitoneal shunt on the 20th day of hospitalization. A subsequent CSF test identified cytomegalovirus (CMV) infection, leading to the initiation of ganciclovir treatment. Despite treatment for CMV encephalitis, the patient continued to exhibit altered sensorium and was re-evaluated with the following tests: magnetic resonance imaging showed significant supratentorial hydrocephalus without CSF transudation and thinning of the white matter; electroencephalogram revealed diffuse slow waves; elevated serum ammonia, and amino acid chromatography indicated reduced citrulline. Protein restriction and sodium benzoate treatment were started. A molecular genetic panel identified a pathogenic variant c.421C>T;p.(Arg141*) in the OTC gene, in heterozygosity.

Discussão

Metabolic etiology should be considered in the investigation of coma in the pediatric age group. OTC deficiency, an enzyme in the urea cycle with X-linked inheritance, has two clinical presentations. The early form occurs in males with acute neonatal encephalopathy, hypothermia and respiratory alkalosis. The late form can occur in both sexes with recurrent vomiting, encephalopathy or psychotic symptoms, and/or epilepsy, often triggered by factors such as infection or protein overload. Diagnosis of OTC deficiency can be suggested by increased urinary orotic acid, hyperammonemia, elevated glutamine and reduced citrulline. Definitive diagnosis is established through molecular investigation and identification of a pathogenic variant in heterozygosity in the OTC gene. The phenotype in heterozygous females can range from asymptomatic to significant symptoms such as recurrent hyperammonemia and neurological impairment, depending on X-chromosome inactivation. Approximately 15% of women become symptomatic over their lifetime.

Comentários finais

OTC deficiency in females can be triggered by infectious processes, protein overload, surgeries, febrile illnesses or prolonged fasting. Clinical manifestations depend on the favorable or unfavorable inactivation of the X-chromosome in hepatocytes.

Referências

Lichter-Konecki, U., Caldovic, L., Morizono, H., Simpson, K., Mew, A., & MacLeod, E. (2022). Ornithine transcarbamylase deficiency.

Elismenes, M. H. (2019, September). Título: Deficiencia de Ornitín Transcarbamilasa: presentación de un caso con fenómeno de inactivación del X. In genetica2019.

Santos, L. G., Alves, O. M. R. P., de Oliveira Lucas, E. L., & Calábria, L. K. (2015). Desordens do metabolismo de aminoácidos e intermediários do ciclo da ureia: uma revisão. Revista de Medicina e Saúde de Brasília, 4(2).

Lopes, F. F. (2019). Perfil clínico e laboratorial de pacientes portadores de Desordens do Ciclo da Ureia: a importância da hiperamonemia.

Palavras Chave

Ornithine Transcarbamylase (OTC) Deficiency; atypical presentation; urea cycle