Metabolic Puzzle: 5-Oxoprolinemia Unmasking a Congenital Disorder of Glycosylation

Dear Editor,

Inborn errors of metabolism are genetic disorders affecting metabolic pathways, with an estimated incidence in India of 1/2,497 live births.¹ We report a 3-day-old male neonate, born full term via spontaneous vaginal delivery to non consanguineous parents, presented with lethargy, poor feeding, and red-colored urine. Birth weight was 2.7 kg, and no dysmorphic features were noted. He was icteric, mildly dehydrated, and tachypneic. Initial management included antibiotics and supportive care, though sepsis screening later returned negative. Laboratory investigations revealed severe anemia (Hb 6.0 g/dL), elevated reticulocyte count, schistocytes, and Heinz bodies indicative of oxidative hemolysis. Blood gas analysis revealed high anion gap metabolic acidosis, characterized by elevated serum lactate and ammonia levels. Urine examination showed hemoglobinuria. Tandem mass spectrometry was normal; however, gas chromatography-mass spectrometry revealed increased urinary 5-oxoproline. The infant was managed with injectable fluids, sodium bicarbonate, and oral antioxidant therapy (vitamins C and E). Exome sequencing confirmed heterozygosity for an uncertain significance ALG8 variant linked with type 1h congenital glycosylation disease. By day 12, the baby showed marked clinical improvement and was discharged with ongoing antioxidant supplementation. At 15 months, the child is thriving well, with normal growth and developmental milestones. Glutathione synthetase deficiency (GSS) is a rare genetic disorder resulting from mutations in the GSS gene, which impairs glutathione production, a key antioxidant that protects cells from oxidative stress.² The deficiency disrupts redox balance and can cause symptoms like hemolytic anemia, developmental delays, and recurrent infections.³ Treatment focuses on symptom management, reducing oxidative stress, and correcting metabolic acidosis. N-acetylcysteine may help boost glutathione levels, though its effectiveness varies. Prognosis depends on severity, early diagnosis, and the success of supportive care.