RESUMO
OBJECTIVE: A retrospective analysis of 74 cases of neonatal-onset ornithine transcarbamylase (OTC) deficiency. METHODS: The medical records of 74 of the 128 male patients referred to this center with neonatal onset OTC from 1976 to 1996 were available and analyzed. RESULTS: Initial symptoms of OTC deficiency were nonspecific and included feeding difficulties, lethargy, and "respiratory distress"; vomiting was infrequent. Respiratory alkalosis was regularly observed; the mean pH and pCO2 were 7.5 and 24 torr, respectively. Early consideration of a metabolic disorder in those neonates with a negative family history was only 9%. Sepsis was initially misdiagnosed in 50% of the cases. For all patients the mean age at onset was 63 hours. Survival was better among those who had later onset, later diagnostic studies, and diagnosis. Apart from 1 patient whose peak ammonium level was 400 micromol/L, all surviving patients had severe developmental delay. CONCLUSIONS: OTC deficiency should be suspected in term infants who have early signs of encephalopathy, particularly after the first 24 hours; a respiratory alkalosis is pathognomic of urea cycle disorders. Severe developmental delay is the usual outcome of OTC deficiency.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/epidemiologia , Amônia/sangue , Doença da Deficiência de Ornitina Carbomoiltransferase , Ureia/metabolismo , Distribuição por Idade , Idade de Início , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/psicologia , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Desenvolvimento Infantil , Terapia Combinada , Humanos , Recém-Nascido , Masculino , Manifestações Neurocomportamentais , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To monitor long-term survival and outcome of patients with neonatal-onset argininosuccinate synthetase deficiency (ASD) who were treated with specific therapeutic protocols designed to activate alternative pathways of waste nitrogen excretion. DESIGN: Patients for this study included 24 infants born before 1990 and rescued from hyperammonemic coma caused by neonatal-onset ASD; they were referred to this center for enrollment in ongoing clinical studies of sodium benzoate, sodium phenylacetate, and sodium phenylbutyrate. Collaborating physicians throughout the United States and Canada provided information on survival, intellectual development, intercurrent hyperammonemic episodes, and anthropometric and biochemical measurements. RESULTS: The cumulative survival rate was 87.5% at 5 years and 72% at 10 years of age. Survivors include 15 patients currently treated with high doses of sodium phenylbutyrate; two patients have withdrawn. Among the treated group, 11 are classified as severely to profoundly mentally retarded. The remaining four patients have IQ measurements in the borderline to mentally retarded range. All patients have had intercurrent hyperammonemic episodes; our data indicate that the frequency of the episodes has decreased with implementation of the current protocol. These patients are growth retarded, but most have height-for-weight z scores within 2 SD of the mean. Laboratory studies of plasma amino acids and of hematopoietic, renal, and hepatic function are within normal limits with the exception of slightly elevated serum aminotransferase values. CONCLUSION: Our results indicate that these drugs are safe and that the current protocol improves survival rates. However, survival is accompanied by mental retardation, growth retardation, risk of hyperammonemic episodes, and the necessity of lifetime adherence to strict medication and dietary management.
Assuntos
Argininossuccinato Sintase/deficiência , Citrulina/sangue , Adolescente , Idade de Início , Aminoácidos/sangue , Antropometria , Argininossuccinato Sintase/sangue , Criança , Pré-Escolar , Protocolos Clínicos , Seguimentos , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etiologia , Estado Nutricional , Taxa de SobrevidaRESUMO
Because increases in plasma glutamine concentrations are almost always associated with hyperammonemia in patients with urea cycle disorders, we determined the correlation between these two variables for 2 years in a child with ornithine transcarbamylase deficiency. A correlation coefficient of 0.77 (p less than 0.0001) was found. Hyperammonemia was rarely observed when plasma glutamine levels were near normal. These data suggest that one goal of therapy is the maintenance of plasma glutamine levels at or near normal values.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/sangue , Amônia/sangue , Glutamina/sangue , Doença da Deficiência de Ornitina Carbomoiltransferase , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Humanos , Recém-Nascido , Masculino , Ureia/metabolismoRESUMO
We present a diagnostic and therapeutic protocol designed to prevent clinical expression of inborn errors of urea synthesis in the neonatal period, and discuss the long-term developmental outcome of survivors. The families of 32 infants, among 43 identified prenatally as being at risk for a urea cycle disorder, chose to have their infants treated according to a diagnostic and therapeutic protocol, beginning at birth. The therapy was effective in avoiding neonatal hyperammonemic coma and death in seven patients with carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, and argininosuccinate lyase deficiency. When treated prospectively, five of eight patients with ornithine transcarbamylase deficiency avoided severe hyperammonemia and survived the neonatal period. Two patients with carbamoyl phosphate synthetase deficiency and two with ornithine transcarbamylase deficiency have subsequently died; three additional patients with the latter disorder have received orthotopic liver transplants. Our experience suggests that these surviving patients have had a more favorable neurologic outcome than patients rescued from neonatal hyperammonemic coma. However, all of them require a burdensome medical regimen and may have handicaps that include impairment of development and recurrent episodes of hyperammonemia. Further, those with deficiency of carbamoyl phosphate synthetase or ornithine transcarbamylase have a high mortality rate.