RESUMO
Eight cases of isolated human pyruvate carboxylase deficiency were examined from seven families. Although all patients presented with a chronic lacticacidemia, two particular patients presented with the added features of hyperammonemia, citrullinemia, and hyperlysinemia. When cultured skin fibroblasts from these patients were examined for their ability to synthesize [3H]biotin-containing proteins, it was found that the two patients who presented with hyperammonemia, citrullinemia, and hyperlysinemia did not synthesise a protein of the correct subunit molecular weight (Mr = 125 K daltons) corresponding to pyruvate carboxylase. In addition, when skin fibroblast proteins were labeled with [35S]methionine, cross-reacting material (CRM) corresponding to pyruvate carboxylase was immunoprecipitated by antipyruvate carboxylase antiserum in most patients, but again the two patients with the atypical presentation showed no CRM. We propose that the different clinical presentation of human pyruvate carboxylase deficiency is a manifestation of two different mutations in the pyruvate carboxylase gene, one that results in the synthesis of a relatively inactive pyruvate carboxylase protein CRM(+ve) and one that results in the lack of expression of the gene in the form of a recognizable protein CRM(-ve).
Assuntos
Piruvato Carboxilase/genética , Biotina/metabolismo , Células Cultivadas , Precipitação Química , Reações Cruzadas , Eletroforese em Gel de Poliacrilamida , Feminino , Fibroblastos/enzimologia , Humanos , Lactente , Recém-Nascido , Masculino , Peso Molecular , Mutação , Piruvato Carboxilase/biossíntese , Doença da Deficiência de Piruvato Carboxilase , Complexo Piruvato Desidrogenase/metabolismo , Pele/citologia , SíndromeAssuntos
Desenvolvimento Infantil , Proteínas Alimentares/administração & dosagem , Fenilcetonúrias/dietoterapia , Complicações na Gravidez/dietoterapia , Adulto , Feminino , Humanos , Recém-Nascido , Deficiência Intelectual/prevenção & controle , Masculino , Fenilalanina/sangue , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da GravidezAssuntos
Fenilcetonúrias/complicações , Complicações na Gravidez , Crânio/crescimento & desenvolvimento , Adulto , Cefalometria , Criança , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Deficiência Intelectual/etiologia , Deficiência Intelectual/genética , Masculino , Troca Materno-Fetal , Fenilcetonúrias/genética , Gravidez , Radiografia , Crânio/diagnóstico por imagem , Crânio/embriologiaRESUMO
Intermittent MSUD in a mother and her daughter is reported. Fibroblast cultures were studied for branched-chain keto acid decarboxylase and results show that the mother has approximately 12% while the daughter has 5% of the normal enzyme activity. Other key members in the family were also studied for enzyme activity. It appears that the child has inherited an abnormal gene from her homozygous mother and another abnormal gene from her heterozygous father.A classification based on the degree of residual enzyme activity and protein tolerance places the mother in grade III and the daughter in grade II category. Classical MSUD, where the enzyme activity is less than 2% of normal, belongs to grade I.
