RESUMO
A patient is described with congenital hypotonia, lax joints, friable skin, hemorrhagic scars, high-arched palate, and borderline microcornea. Acid hydrolyzed whole skin collagen had a reduced hydroxylysine content of 0.5 residues per 1,000 as compared to 5.1 +/- 0.7 in control skin. Collagen lysyl hydroxylase in dialyzed subcellular fractions of cultured skin fibroblasts required L-ascorbate as a principal cofactor. Activity of this enzyme in cultured skin fibroblasts derived from this patient, his father, and mother were 17%, 66%, and 39% of control values, respectively. Collagen prolyl hydroxylase activity was normal. Pharmacologic amounts of oral vitamin C (4 gm/day) produced an increase and withdrawal resulted in abrupt diminution of urinary excretion of hydroxylysine. Over a two-year period the patient's wound healing and muscle strength improved and corneal diameter increased. Hydroxylysine content of the skin did not increase.
Assuntos
Ácido Ascórbico/uso terapêutico , Síndrome de Ehlers-Danlos/genética , Oxigenases de Função Mista/deficiência , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/deficiência , Criança , Ensaios Enzimáticos Clínicos , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/tratamento farmacológico , Feminino , Fibroblastos/enzimologia , Humanos , Hidroxilisina/metabolismo , Hidroxilisina/urina , Masculino , Pele/enzimologiaRESUMO
Biochemical and morphologic studies on a patient with glutaric aciduria are presented. Generalized aminoaciduria, alpha-aminoadipic aciduria, and saccharopinuria were noted just prior to death, as well as glutaconic aciduria greater than beta-hydroxyglutaric aciduria. Mutant liver mitochondria did not oxidize glutaryl-CoA to glutaconyl-CoA, indicating deficiency of glytaryl-CoA dehydrogenase. Autopsy revealed cerebral edema, ischemic neuronal changes, and striatal degeneration in the brain with fatty changes in liver, kidney, and myocardium.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/patologia , Glutaratos/urina , Oxirredutases/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/urina , Autopsia , Encéfalo/patologia , Química Encefálica , Criança , Glutaratos/análise , Humanos , Hidroxilisina/metabolismo , Lactente , Rim/patologia , Fígado/patologia , Lisina/metabolismo , Masculino , Mitocôndrias Hepáticas/metabolismo , Miocárdio/patologia , Triptofano/metabolismoRESUMO
In two siblings with dystonic cerebral palsy the urinary metabolic profiles of organic acids were dominated by glutaric acid, a metabolite not normally present in urine. The exretion of glutaric acid amounted to several grams per day. The urinary excretion of beta-OH-glutaric acid and glutaconic acid was also enhanced. Imparied metabolism of glutaryl-CoA by leukocytes indicates that the patients suffer from an inborn error of lysine, tryptophan, and hydroxylysine metabolism. A defective oxidation of glutaryl-CoA to crotonyl-CoA, probably due to a deficiency of glutaryl-CoA dehydrogenase, is consistent with these findings.