Rare Yet Reversible: CA5A Deficiency Presenting as Neonatal Metabolic Crisis

Abstract

Carbonic anhydrase 5A (CA5A) deficiency (OMIM 615751) is a rare autosomal recessive metabolic disorder caused by mutations in the CA5A gene on chromosome 16q24.2. Deficiency of this mitochondrial enzyme disrupts bicarbonate production, impairing ureagenesis and energy metabolism, and typically presents in neonates with hyperammonemic encephalopathy, lactic acidosis, and hypoglycemia. We report a term neonate who developed severe hyperammonemia with encephalopathy on day 4 of life, requiring peritoneal dialysis, nitrogen scavengers, and ventilatory support. Tandem mass spectrometry and urinary GCMS were non-diagnostic, but singleton exome sequencing identified a homozygous CA5A variant, c.721G>A (p.Glu241Lys), classified as likely pathogenic. With early intervention, the infant recovered fully and remains metabolically stable with normal growth and neurodevelopment at 5 years of age. This case underscores the diagnostic challenge of CA5A deficiency, highlights the role of exome sequencing, and demonstrates the potential for excellent long-term outcomes with timely recognition and management.