RESUMO
Identical studies using stable isotopes were performed before and after a 3-day trial of oral N-carbamyl-l-glutamate (NCG) in 5 subjects with late-onset carbamyl phosphate synthetase deficiency. NCG augmented ureagenesis and decreased plasma ammonia in 4 of 5 subjects. There was marked improvement in nitrogen metabolism with long-term NCG administration in 1 subject.
Assuntos
Doença da Deficiência da Carbamoil-Fosfato Sintase I/tratamento farmacológico , Glutamatos/uso terapêutico , Glutamina/sangue , Ureia/metabolismo , Adolescente , Adulto , Amônia/sangue , Doença da Deficiência da Carbamoil-Fosfato Sintase I/sangue , Criança , Pré-Escolar , Feminino , Humanos , Modelos Lineares , Masculino , Espectrometria de Massas , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To compare the clinical course and outcome of patients diagnosed with one of 4 neonatal-onset urea cycle disorders (UCDs): deficiency of carbamyl phosphate synthase 1 (CPSD), ornithine transcarbamylase (OTCD), argininosuccinate synthase (ASD), or argininosuccinate lyase (ALD). STUDY DESIGN: Clinical, biochemical, and neuropsychological data from 103 subjects with neonatal-onset UCDs were derived from the Longitudinal Study of Urea Cycle Disorders, an observational protocol of the Urea Cycle Disorders Consortium, one of the Rare Disease Clinical Research Networks. RESULTS: Some 88% of the subjects presented clinically by age 7 days. Peak ammonia level was 963 µM in patients with proximal UCDs (CPSD or OTCD), compared with 589 µM in ASD and 573 µM in ALD. Roughly 25% of subjects with CPSD or OTCD, 18% of those with ASD, and 67% of those with ALD had a "honeymoon period," defined as the time interval from discharge from initial admission to subsequent admission for hyperammonemia, greater than 1 year. The proportion of patients with a poor outcome (IQ/Developmental Quotient <70) was greatest in ALD (68%), followed by ASD (54%) and CPSD/OTCD (47%). This trend was not significant, but was observed in both patients aged <4 years and those aged ≥ 4 years. Poor cognitive outcome was not correlated with peak ammonia level or duration of initial admission. CONCLUSION: Neurocognitive outcomes do not differ between patients with proximal UCDs and those with distal UCDs. Factors other than hyperammonemia may contribute to poor neurocognitive outcome in the distal UCDs.
Assuntos
Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Distúrbios Congênitos do Ciclo da Ureia/complicaçõesRESUMO
In a patient with N-acetylglutamate synthase (NAGS) deficiency, incorporation of an isotopic label from ammonium chloride into urea was markedly reduced before treatment with N-carbamyl-L-glutamate (NCLG) and completely normalized following treatment. Blood ammonia rose following ammonium tracer ingestion before treatment but remained low following treatment. Serum urea concentration doubled following the treatment.