RESUMO
The long-term treatment of patients with urea cycle disorders (UCDs) includes diet treatment and use of specific medications. Guidelines are provided for patients with a severe phenotype. However, treatment must be tailored for each individual, especially with regard to residual enzyme function and in vivo metabolic capacity. This will be reflected in tests used for monitoring therapy that should be performed on a periodic basis. The goal of therapy is to eliminate chronic complications, a laudable but rarely attainable goal. Sick-day rules are discussed. Chronic management also includes diverse services that are essential to the success of the metabolic program. These include neurologic and developmental evaluations, feeding team evaluation and therapy, physical and occupational therapies, speech therapy, school and educational services, social service intervention, psychologic services, and genetic counseling.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/terapia , Ureia/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/dietoterapia , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Arginina/uso terapêutico , Carbamoil-Fosfato Sintase (Amônia)/deficiência , Citrulina/uso terapêutico , Proteínas Alimentares/administração & dosagem , Humanos , Hiperamonemia/metabolismo , Hiperamonemia/terapia , Doença da Deficiência de Ornitina Carbomoiltransferase , Fenilbutiratos/uso terapêuticoRESUMO
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.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/prevenção & controle , Argininossuccinato Sintase/deficiência , Acidúria Argininossuccínica , Carbamoil-Fosfato Sintase (Amônia)/deficiência , Doença da Deficiência de Ornitina Carbomoiltransferase , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Amônia/sangue , Antropometria , Criança , Pré-Escolar , Protocolos Clínicos , Deficiências do Desenvolvimento , Seguimentos , Humanos , Lactente , Recém-Nascido , Análise de Sobrevida , Ureia/sangueAssuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Amônia/sangue , Carbamoil-Fosfato Sintase (Amônia)/deficiência , Citrulina/sangue , Ureia/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/dietoterapia , Biomarcadores/sangue , Humanos , Recém-Nascido , MasculinoAssuntos
Argininossuccinato Sintase/deficiência , Acidúria Argininossuccínica , Carbamoil-Fosfato Sintase (Amônia)/deficiência , Triagem de Portadores Genéticos , Ligases/deficiência , Liases/deficiência , Doença da Deficiência de Ornitina Carbomoiltransferase , Alanina , Amônia/sangue , Reações Falso-Positivas , Humanos , Ácido Orótico/urina , ProteínasRESUMO
Se presenta un paciente que padece de hiperamoniemia congénita por déficit enzimático del ciclo de la urea. Se plantea por las características clinicohumorales que sea debido a un déficit parcial de carbamilfosfato sintetasa. Se hacen comentarios al respecto
Assuntos
Lactente , Humanos , Masculino , Carbamoil-Fosfato Sintase (Amônia)/deficiênciaRESUMO
We reviewed clinical data in 33 patients with transient hyperammonemia of the newborn (THAN): six previously unreported cases and 27 from the literature. Thirteen neonates with urea cycle enzyme deficiencies (UCED) served for comparison. No differences were found in the incidence of perinatal complications, route of delivery, Apgar scores, sex, or incidence or time of onset of seizures. On the other hand, neonates with THAN had significantly lower birth weights (mean +/- SEM 2282 +/- 78 gm vs 3336 +/- 222 gm, P less than 0.001) and gestational ages (35.1 +/- 0.5 weeks vs 39.6 +/- 0.5 weeks, P less than 0.001). Mean time of onset of respiratory distress (3.9 +/- 1.4 hours vs 71.5 +/- 26.1 hours, P less than 0.001), ventilatory support (P less than 0.001), lethargy (P less than 0.005), and coma (P less than 0.005) occurred earlier in THAN. Distinctive laboratory findings in patients with THAN included abnormal chest radiographic findings and plasma ammonium concentrations that were higher (1871 +/- 209 microM vs 973 +/- 169 microM, P less than 0.02) at an earlier age. Respiratory distress occurred in all but one patient with THAN before 24 hours; in contrast, only 62% of infants with UCED had respiratory symptoms, and none before 30 hours. In this retrospective study, the clinical presentation alone differentiated THAN from UCED.