RESUMO
Ornithine transcarbamylase deficiency is an X-linked recessive disorder of urea biosynthesis characterized by recurrent, often fatal, hyperammonemic encephalopathy in affected males; carrier females are usually asymptomatic. We report here the clinical and laboratory findings in five symptomatic heterozygous females with ornithine transcarbamylase deficiency. In each case, the onset of symptoms occurred in the 1st year of life, but diagnosis was delayed by up to 15 years. Symptoms included recurrent vomiting with lethargy (five patients), dietary protein intolerance (five), irritability (four), severe acute encephalopathy (three), ataxia (three), and acute hemiparesis (two). All eventually showed evidence of developmental delay or learning difficulties. Two of the three who experienced severe, acute, hyperammonemic encephalopathy suffered serious, permanent neurologic sequelae. Three of the patients showed decreased ornithine transcarbamylase activity in liver obtained by needle biopsy, and the other two had marked orotic aciduria associated with hyperammonemia. Neuroimaging studies demonstrated persistent abnormal lobar attenuation and abnormal signal on computed tomographic scan and magnetic resonance imaging. All patients showed marked symptomatic improvement on treatment with dietary protein restriction supplemented by pharmacologic measures to increase nonprotein nitrogen excretion. Ornithine transcarbamylase deficiency should be considered in the differential diagnosis of acute or chronic encephalopathy in females at any age.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Amônia/sangue , Encefalopatias Metabólicas/genética , Doença da Deficiência de Ornitina Carbomoiltransferase , Aberrações dos Cromossomos Sexuais/genética , Cromossomo X , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/dietoterapia , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Encéfalo/patologia , Dano Encefálico Crônico/diagnóstico , Dano Encefálico Crônico/enzimologia , Dano Encefálico Crônico/genética , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/dietoterapia , Encefalopatias Metabólicas/enzimologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Proteínas Alimentares/administração & dosagem , Feminino , Seguimentos , Triagem de Portadores Genéticos , Humanos , Lactente , Imageamento por Ressonância Magnética , Exame Neurológico , Tomografia Computadorizada por Raios XRESUMO
The clinical, radiologic, neurophysiologic, and pathologic findings in 10 children with histologically proven Alexander's disease are described, and the presence of two broad clinical subgroups is confirmed. Macrocephaly, regression, and seizures are found in the infantile form, whereas bulbar signs predominate the so-called juvenile form. None of the clinical or neurophysiologic findings is pathognomonic, and radiologic features suggesting the diagnosis are not present in all cases. However, the combination of abnormalities may suggest the diagnosis and justify histologic confirmation.
Assuntos
Hidrocefalia/diagnóstico , Deficiência Intelectual/diagnóstico , Crânio/anormalidades , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Pré-Escolar , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Hidrocefalia/genética , Hidrocefalia/fisiopatologia , Lactente , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Masculino , Microscopia Eletrônica , Neurofibrilas/ultraestrutura , Exame NeurológicoRESUMO
We report two cousins, born to consanguineous parents, with an alopecia-mental retardation syndrome and the additional features of microcephaly and epilepsy. Similar reported cases are reviewed and genetic heterogeneity is suggested.
Assuntos
Anormalidades Múltiplas/genética , Alopecia/genética , Epilepsia/genética , Deficiência Intelectual/genética , Microcefalia/genética , Humanos , Lactente , Masculino , LinhagemRESUMO
We describe a family with distal spinal muscular atrophy and vocal cord paralysis, similar to the condition reported by Young and Harper in 1980. Both pedigrees are consistent with autosomal dominant inheritance.
Assuntos
Atrofia Muscular Espinal/genética , Paralisia das Pregas Vocais/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genes Dominantes/genética , Humanos , Masculino , Atrofia Muscular Espinal/patologia , Linhagem , Síndrome , Paralisia das Pregas Vocais/patologiaRESUMO
Two sibs are reported with Ramon syndrome with the previously undescribed associations of insulin dependent diabetes mellitus and vascular skin lesions.
