RESUMEN
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.
Asunto(s)
Ácido Ascórbico/uso terapéutico , Síndrome de Ehlers-Danlos/genética , Oxigenasas de Función Mixta/deficiencia , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/deficiencia , Niño , Pruebas Enzimáticas Clínicas , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/tratamiento farmacológico , Femenino , Fibroblastos/enzimología , Humanos , Hidroxilisina/metabolismo , Hidroxilisina/orina , Masculino , Piel/enzimologíaRESUMEN
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.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/patología , Glutaratos/orina , Oxidorreductasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/orina , Autopsia , Encéfalo/patología , Química Encefálica , Niño , Glutaratos/análisis , Humanos , Hidroxilisina/metabolismo , Lactante , Riñón/patología , Hígado/patología , Lisina/metabolismo , Masculino , Mitocondrias Hepáticas/metabolismo , Miocardio/patología , Triptófano/metabolismoRESUMEN
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.