RESUMO
Two girls and one boy are described, with severe infantile parkinsonism-dystonia. This syndrome is usually caused by endogenous dopamine deficiency but in these patients was associated with elevated dopamine metabolites in CSF and an unusual eye movement disorder: ocular flutter together with saccade initiation failure. Pyramidal tract signs also emerged in the course of the disease in two patients. This combination of symptoms and biochemical findings suggests a unique pathogenic mechanism.
Assuntos
Dopamina/líquido cefalorraquidiano , Distúrbios Distônicos/líquido cefalorraquidiano , Ácido Homovanílico/líquido cefalorraquidiano , Transtornos da Motilidade Ocular/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , Dopamina/urina , Distúrbios Distônicos/diagnóstico por imagem , Feminino , Ácido Homovanílico/urina , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Recém-Nascido , Masculino , Transtornos da Motilidade Ocular/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Reflexo Anormal , Movimentos Sacádicos , Síndrome , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
A full-length cDNA clone encoding human beta-ureidopropionase was isolated. A 1152-nucleotide open reading frame which corresponds to a protein of 384 amino acids with a calculated molecular weight of 43¿ omitted¿158 Da, surrounded by a 5'-untranslated region of 61 nucleotides and a 3'-untranslated region of 277 nucleotides was identified. The protein showed 91% similarity with the translation product of the rat beta-ureidopropionase cDNA. Expression of the human cDNA in an Escherichia coli and eukaryotic COS-7 expression system revealed a very high beta-ureidopropionase enzymatic activity, thus confirming the identity of the cDNA. Since human EST libraries from brain, liver, kidney and heart contained partial beta-ureidopropionase cDNAs, the enzyme seems to be expressed in these tissues, in agreement with the expression profile of this enzyme in rat. Using the human cDNA as a probe a genomic P1 clone could be isolated containing the complete human beta-ureidopropionase gene. The gene consist of 11 exons spanning approximately 20 kB of genomic DNA. Fluorescence in situ hydridization localized the human beta-ureidopropionase gene to 22q11.2.