ABSTRACT
Glutathione synthetase deficiency (GSSD) is a rare inborn error of glutathione metabolism with autosomal recessive inheritance. The severe form of the disease is characterized by acute metabolic acidosis, usually present in the neonatal period with hemolytic anemia and progressive encephalopathy. A case of a male newborn infant who had severe metabolic acidosis with high anion gap, hemolytic anemia, and hyperbilirubinemia is reported. A high level of 5-oxoproline was detected in his urine and a diagnosis of generalized GSSD was made. DNA sequence analysis revealed the infant to be compound heterozygous with two mutations, c.738dupG in exon 8 of GSS gene resulting in p.S247fs and a repetitive sequence in exon 3 of GSS gene. Treatment after diagnosis of GSSD included supplementation with antioxidants and oral sodium hydrogen bicarbonate. However, he maintained a variable degree of metabolic acidosis and succumbed shortly after his parents requested discontinuation of therapy because of dismal prognosis and medical futility when he was 18 days old.
Subject(s)
Humans , Male , Infant, Newborn , Amino Acid Metabolism, Inborn Errors/genetics , Glutathione Synthase/deficiency , Mutation , Acidosis/etiology , Amino Acid Metabolism, Inborn Errors/metabolism , Glutamic Acid/analysis , Glutathione Synthase/genetics , Glutathione Synthase/metabolism , Pyroglutamate Hydrolase/deficiency , Pyroglutamate Hydrolase/genetics , Sequence Analysis, DNA/methodsABSTRACT
Pyroglutamic acid (also known as 5-oxoproline) is an organic acid intermediate of the gamma-glutamyl cycle. Accumulation of pyroglutamic acid is a rare cause of high anion gap metabolic acidosis. In the pediatric population, the congenital form of pyroglutamic acidemia has been extensively described. However, there are scarce reports of the acquired form of this condition in children. The urine test for organic acids confirms the diagnosis of pyroglutamic acidemia. We report the case of a 16-month-old girl who developed transient 5-oxoprolinemia associated with malnutrition and the use of acetaminophen and ampicillin for the treatment of acute otitis media and abdominal pain. The patient received 21-hour course of n-acetylcysteine with improvement of metabolic acidosis. This report highligts the need of considering pyroglutamic acidemia in the differencial diagnosis for high anion gap metabolic acidosis in pediatric patients with malnutrition and other risk factors...
Subject(s)
Humans , Glutathione Synthase/deficiency , Ketosis , Pyrrolidonecarboxylic AcidABSTRACT
Se estandarizaron las técnicas de actividad de g -glutamil cisteil sintetasa y glutatión sintetasa con el objetivo de estudiar los pacientes con deficiencia congénita de glutatión reducido. Los valores normales encontrados en nuestro laboratorio no presentaron diferencias significativas con los señalados por otros autores. Se estudiaron varios miembros de una familia con deficiencia de glutatión reducido. Los estudios bioquímicos excluyeron la posible deficiencia de glucosa-6-fosfato deshidrogenasa. En el propósito y un hermano (G.D.R.) se encontró deficiencia de glutatión sintetasa. Ambos presentan una anemia hemolítica congénita no esferocítica, con hemólisis crónica e íctero que se exacerba en el transcurso de procesos infecciosos y también litiasis vesicular. Ninguno presentó acidosis metabólica ni trastornos neurológicos progresivos, por lo que ambos son portadores de la forma benigna de la enfermedad. En el padre y otro hermano, los resultados del estudio hematológico y bioquímico indican que posiblemente son heterocigóticos para la deficiencia de esta enzima. Esta es la primera familia con deficiencia de glutatión sintetasa encontrada en nuestra población