Hemolytic anemia (HA) of the newborn should be considered in cases of rapidly developing, severe, or persistent
hyperbilirubinemia. Several causes of corpuscular
hemolysis have been described, among which red blood cell
enzyme defects are of particular concern. We report a rare case of red blood cell
enzyme defect in a male infant, who presented during his first months of life with recurrent and isolated neonatal
hemolysis. All main causes were ruled out. At 6.5 months of age, the patient presented with
gastroenteritis requiring hospitalization; fortuitously, urine organic
acid chromatography revealed a large peak of
5-oxoproline. Before the association between HA and
5-oxoprolinuria was noted,
glutathione synthetase deficiency was suspected and confirmed by a low
glutathione synthetase concentration and a collapse of
glutathione synthetase activity in erythrocytes. Moreover, molecular diagnosis revealed 2 mutations in the
glutathione synthetase gene: a previously reported missense mutation (c.[656A>G]; p.[Asp219Gly]) and a mutation not yet described in the binding site of the
enzyme (c.[902T>C]; p.[Leu301Pro]). However, 15 days later, a control sample revealed no signs of
5-oxoprolinuria and the clinical history discovered administration of
acetaminophen in the 48 hours before hospitalization. Thus, in this patient,
acetaminophen exposure allowed the diagnosis of a mild form of
glutathione synthetase deficiency, characterized by isolated HA. Early diagnosis is important because treatment with
bicarbonate,
vitamins C and E, and elimination of trigger factors are recommended to improve long-term outcomes.
Glutathione synthetase deficiency should be screened for in cases of unexplained newborn HA.