RESUMO
Adenylosuccinate lyase deficiency is an autosomal-recessive disorder of the purine de novo synthesis pathway, diagnosed up to now in approximately 40 patients. The clinical presentation is characterized by severe neurologic involvement including seizures, developmental delay, hypotonia, and autistic features. Neonatal seizures and a severe infantile epileptic encephalopathy are often the first manifestations of this disorder. The existence of genetic heterogeneity for the adenylosuccinate lyase defect could account for variability of the clinical presentation. Deficiency of purine nucleotides, impairment of energy metabolism, and toxic effects are potential mechanisms of cerebral damage. Laboratory investigations show the presence in urine and cerebrospinal fluid of succinylpurines, which are normally undetectable. Currently, no effective treatment is available for adenylosuccinate lyase deficiency. A search for this disorder should be included in the screening program of children with unexplained neonatal seizures or severe infantile epileptic encephalopathy.
Assuntos
Adenilossuccinato Liase/deficiência , Adenilossuccinato Liase/genética , Encéfalo/enzimologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/metabolismo , Metabolismo Energético/fisiologia , Epilepsia/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Nucleotídeos de Purina/urinaAssuntos
Frutose/metabolismo , Gota/urina , Ácido Úrico/sangue , Adenina , Trifosfato de Adenosina/sangue , Idoso , Alopurinol/farmacologia , Eritrócitos/análise , Eritrócitos/enzimologia , Jejum , Glucose/metabolismo , Guanina , Humanos , Hipoxantinas , Lactatos/sangue , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Pessoa de Meia-Idade , Pentosiltransferases/sangue , Fosfatos/sangue , Nucleotídeos de Purina/urina , Purinas/urina , Ribose/sangue , Ácido Úrico/urinaAssuntos
Adenosina Desaminase/deficiência , Transplante de Medula Óssea , Síndromes de Imunodeficiência/terapia , Nucleosídeo Desaminases/deficiência , Nucleotídeos de Purina/sangue , Adenosina Desaminase/sangue , Desoxiadenosinas/urina , Eritrócitos/metabolismo , Antígenos HLA/imunologia , Humanos , Síndromes de Imunodeficiência/metabolismo , Lactente , Linfócitos/metabolismo , Masculino , Nucleotídeos de Purina/urinaRESUMO
To delineate the normal function of purine nucleoside phosphorylase and to understand the pathogenesis of the immune dysfunction associated with deficiency of this enzyme, we studied purine metabolism in a patient deficient in purine nucleoside phosphorylase, her erythrocytes and cultured fibroblasts. She exhibited severe hypouricemia and hypouricosuria but excreted excessive amounts of purines in her urine, the major components of which were inosine and guanosine. Her urine also contained deoxyinosine, deoxyguanosine and uric acid 9-N riboside. The patient's erythrocytes but not her cultured fibroblasts contained increased concentrations of phosphoribosylpyrophosphate and inosine. The metabolic abnormalities resembled those in the erythrocytes of patients with the Lesch-Nyhan syndrome. Purine nucleoside phosphorylase is a necessary component of the major, if not the sole, pathway for the conversion of purine nucleosides and nucleotides to uric acid. The increased intracellular concentrations of inosine may, by inhibiting adenosine deaminase, be related to the immunologic dysfunction.