RESUMO
A 45-month-old girl with 5-oxoprolinuria (pyroglutamic aciduria), hemolysis, and marked glutathione depletion caused by deficiency of glutathione synthetase was followed before and during treatment with ascorbate or N-acetylcysteine. High doses of ascorbate (0.7 mmol/kg per day) or N-acetylcysteine (6 mmol/kg per day) were given for 1 to 2 weeks without any obvious deleterious side effects. Ascorbate markedly increased lymphocyte (4-fold) and plasma (8-fold) levels of glutathione. N-Acetylcysteine also increased lymphocyte (3.5-fold) and plasma (6-fold) levels of glutathione. After these treatments were discontinued, lymphocyte and plasma glutathione levels decreased rapidly to pretreatment levels. Ascorbate treatment was extended for 1 year, and lymphocyte (4-fold) and plasma (2- to 5-fold) glutathione levels remained elevated above baseline. In parallel, the hematocrit increased from 25.4% to 32.6%, and the reticulocyte count decreased from 11% to 4%. The results demonstrate that ascorbate and N-acetylcysteine can decrease erythrocyte turnover in patients with hereditary glutathione deficiency by increasing glutathione levels.
Assuntos
Acetilcisteína/uso terapêutico , Ácido Ascórbico/uso terapêutico , Glutationa Sintase/deficiência , Pré-Escolar , Feminino , Glutationa Sintase/análise , Glutationa Sintase/sangue , Humanos , Linfócitos/enzimologia , Erros Inatos do Metabolismo/sangue , Erros Inatos do Metabolismo/tratamento farmacológico , Vitamina E/uso terapêuticoRESUMO
We describe a relatively new syndrome in four children with characteristic facial dysmorphism, sensorineural hearing loss, severe visual impairment with retinitis pigmentosa, hypotonia, hepatomegaly, and severe developmental delay. Two patients had intracranial hemorrhage secondary to a vitamin K-responsive clotting defect; both had steatorrhea. Liver biopsy specimens in two children showed an accentuated lobular architecture with prominent fibrous bands in the portal area. In one, the ultrastructure showed accumulation of abnormal substances and occasional trilaminar structures in hepatocytes and other cells. All four patients had elevated serum phytanic acid concentrations (0.3 to 2.7 mg/dl, normal less than 0.2 mg/dl) and deficient fibroblast phytanic acid oxidase activity (0.1 to 6.7 pmol/mg protein/hr, normal 23 to 87 pmol/mg protein/hr). Serum pipecolic acid was 7 to 55 times normal, and the ratio of C26/C22 very long chain fatty acids was increased (0.10 to 0.22; normal less than 0.03). This characteristic syndrome has been described in several children and called infantile Refsum disease or phytanic acid storage disease. Its relationship to neonatal adrenoleukodystrophy, hyperpipecolic acidemia, and Zellweger syndrome is discussed.
Assuntos
Ácidos Eicosanoicos/deficiência , Ácidos Graxos/sangue , Oxigenases de Função Mista , Oxirredutases/deficiência , Ácido Fitânico/deficiência , Ácidos Pipecólicos/sangue , Doença de Refsum/diagnóstico , Criança , Pré-Escolar , Deficiências do Desenvolvimento/metabolismo , Diagnóstico Diferencial , Feminino , Fibroblastos/enzimologia , Perda Auditiva Neurossensorial/metabolismo , Hepatomegalia/metabolismo , Humanos , Recém-Nascido , Fígado/metabolismo , Fígado/patologia , Masculino , Tono Muscular , Ácido Fitânico/sangue , Retinose Pigmentar/metabolismo , SíndromeRESUMO
A premature infant presented with elevated concentrations of tyrosine in blood and urine, evidence of hepatocellular damage, demineralization of the bones, and a renal Fanconi syndrome. This is the clinical picture found in hereditary tyrosinemia. The infant also had a perinatal infection with cytomegalovirus.