Neonatal 5-oxoprolinuria: difficult-to-diagnose?

Area of Science:

• Biochemistry
• Pediatrics
• Medical Genetics

Background:

• 5-Oxoprolinuria is a rare inherited metabolic disorder.
• It is caused by a deficiency in glutathione synthetase.
• This deficiency leads to the accumulation of 5-oxoproline and can cause severe health issues.

Observation:

• A male newborn presented with metabolic acidosis and hemolytic anemia.
• Initial suspicion of renal tubular acidosis was made, but further investigation was prompted by developmental delay and ataxia at age two.
• Gas-liquid chromatography and mass spectrometry identified 5-oxoprolinuria.

Findings:

• Erythrocyte glutathione levels were 25% of control values.
• Erythrocyte glutathione synthetase activity was markedly reduced to 5% of control values.
• The patient exhibited neonatal metabolic acidosis, hemolytic anemia, and later developmental delay and ataxia.

Implications:

• The study highlights the importance of considering 5-oxoprolinuria in neonates with metabolic acidosis and hemolytic anemia, especially when amino aciduria is absent.
• It recommends screening for blood glutathione and urine 5-oxoproline in such cases.
• Confirmation via glutathione synthetase assay is crucial for diagnosing neonatal 5-oxoprolinuria and enabling early management.