# Clinical, biochemical, and molecular profiles of three Sri Lankan neonates with pyruvate carboxylase deficiency

## TL;DR

This paper reports on three Sri Lankan neonates with pyruvate carboxylase deficiency, highlighting overlapping clinical and biochemical features and the importance of early diagnosis.

## Contribution

The study adds to the understanding of overlapping phenotypes in pyruvate carboxylase deficiency through a novel genetic variant and clinical observations.

## Key findings

- Three neonates with pyruvate carboxylase deficiency showed overlapping clinical and biochemical features.
- A novel homozygous variant c.2746G>C [p.(Asp916His)] in the PC gene was identified in one proband.
- Early recognition of symptoms is critical for effective patient management and family counseling.

## Abstract

Pyruvate carboxylase, a mitochondrial enzyme, catalyses the conversion of glycolytic end-product pyruvate to tricarboxylic acid cycle intermediate, oxaloacetate. Rare pyruvate carboxylase deficiency manifests in three clinical and biochemical phenotypes: neonatal onset type A, infantile onset type B and a benign C type. The objective of this case series is to expand the knowledge of overlapping clinical and biochemical phenotypes of pyruvate carboxylase deficiency.

We report three Sri Lankan neonates including two siblings, of two unrelated families with pyruvate carboxylase deficiency. All three developed respiratory distress within the first few hours of birth. Two siblings displayed typical biochemical findings reported in type B. The other proband with normal citrulline, lysine, moderate lactate, paraventricular cystic lesions, bony deformities, and a novel missense, homozygous variant c.2746G>C [p.(Asp916His)] in the PC gene, biochemically favoured type A.

Our findings indicate the necessity of prompt laboratory investigations in a tachypneic neonate with coexisting metabolic acidosis, as early recognition is essential for patient management and family counselling. Further case studies are required to identify overlapping symptoms and biochemical findings in different types of pyruvate carboxylase deficiency phenotypes.