RESUMO
OBJECTIVE: A cohort of women with phenylketonuria (PKU) were selected to explore the impact of phenylalanine (Phe) levels and other factors on congenital heart defects (CHDs), microcephaly, and development of their offspring. STUDY DESIGN: Three hundred fifty-four women with PKU were followed up weekly with diet records, blood Phe levels, and sonograms obtained at 18 to 20 and 32 weeks' gestation. At birth, 413 offspring were examined and followed up at 6 months and annually by means of Bayley Mental Developmental Index and Psychomotor Developmental Index tests at 1 and 2 years. The women had Wechsler Adult Intelligence Scales and DNA testing. RESULTS: Thirty-one offspring had CHDs; of these, 17 also had microcephaly. Mean Phe levels at 4 to 8 weeks' gestation predicted CHDs (P <.0001). An infant with a CHD had a 3-fold risk of having microcephaly when the mother had higher Phe levels (P =.02). The Bayley Mental Developmental Index and Psychomotor Developmental Index scores correlated with both CHDs (P =.037 and.0015, respectively) and microcephaly (P =.0001 for both). No direct relationship to the PKU mutation was found. CONCLUSION: None of the women whose offspring had CHDs had blood Phe levels in control during the first 8 weeks of gestation. Women with PKU need to be well controlled on a low-phenylalanine diet before conception and throughout pregnancy.
Assuntos
Deficiências do Desenvolvimento/etiologia , Cardiopatias Congênitas/etiologia , Microcefalia/etiologia , Fenilcetonúrias/complicações , Complicações na Gravidez , Adulto , Desenvolvimento Infantil/fisiologia , Estudos de Coortes , Dieta , Feminino , Seguimentos , Genótipo , Idade Gestacional , Humanos , Recém-Nascido , Inteligência/fisiologia , Prontuários Médicos , Mutação/genética , Fenilalanina/efeitos adversos , Fenilalanina/sangue , Fenilalanina/uso terapêutico , Fenilcetonúrias/genética , Fenilcetonúrias/prevenção & controle , Cuidado Pré-Concepcional , Gravidez , Complicações na Gravidez/prevenção & controle , Desempenho Psicomotor/fisiologia , Fatores de Risco , Ultrassonografia Pré-NatalRESUMO
Establishing the basic defect in Canavan disease has led to reliable biochemical methods for the diagnosis of this disease. The isolation of the gene and identification of mutations causing Canavan disease have led to the possibility of using DNA methods for the diagnosis of Canavan disease and for carrier detection. A surprising finding is the high carrier frequency of this gene defect among Ashkenazi Jewish people. Analysis for two mutations leads to the identification of 97% of Jewish patients with Canavan disease, and screening of Ashkenazi Jews is possible. N-Acetylaspartic acid has been considered to be an inert compound. The pathophysiology of Canavan disease links lack of NAA hydrolysis to a severe, debilitating white matter disease. Currently, NAA is being studied in many other brain disorders, such as Alzheimer disease, Huntington disease, and stroke. However, the only disease with a specific defect in the metabolism of NAA is Canavan disease. An animal model for Canavan disease is needed to study some of the questions regarding the role of NAA in brain tissue, and for the study of therapeutic modalities, including gene therapy.
Assuntos
Encéfalo/patologia , Doença de Canavan/diagnóstico , Idade de Início , Ácido Aspártico/análogos & derivados , Ácido Aspártico/urina , Encéfalo/enzimologia , Encéfalo/ultraestrutura , Doença de Canavan/enzimologia , Doença de Canavan/genética , Criança , Diagnóstico Diferencial , Humanos , Judeus , Imageamento por Ressonância Magnética , Masculino , Hipotonia Muscular , Degeneração Neural , Diagnóstico Pré-Natal , Taxa de SobrevidaRESUMO
A patient with neonatal citrullinemia caused by severe deficiency of argininosuccinate synthetase was treated prospectively according to the currently accepted protocol. We gradually reduced the doses and then discontinued treatment with sodium benzoate and phenylacetate; blood glutamine levels were maintained in the normal range, but ammonia was mildly elevated. Growth and development progressed normally through 31 months of age. Some patients with citrullinemia can be successfully managed without daily sodium benzoate and phenylacetate therapy.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Citrulina/sangue , Erros Inatos do Metabolismo dos Aminoácidos/fisiopatologia , Amônia/sangue , Arginina/sangue , Arginina/uso terapêutico , Argininossuccinato Sintase/deficiência , Benzoatos/uso terapêutico , Ácido Benzoico , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Fenilacetatos/uso terapêuticoRESUMO
An 8-month-old boy with severe lactic acidosis was found to have lipoamide dehydrogenase deficiency. Treatment with thiamine, biotin, bicarbonate, protein restriction, and ketogenic diet failed to alleviate the lactic acidosis. Oral administration of lipoic acid 25 to 50 mg/kg produced dramatic improvement in lactic and pyruvic acidemia, which has continued for 2 years and which has been accompanied by clinical improvement.