Novel HADHA Mutation Causes Mitochondrial Protein Deficiency and Neuromuscular Disease

Abstract

Mitochondrial trifunctional protein deficiency (MTP deficiency) is a rare genetic disorder affecting oxidation of long-chain fatty acids. It typically causes severe neonatal symptoms like heart/liver disease, hypoglycemia, and metabolic acidosis. It can also gradually present with peripheral neuropathy, episodic rhabdomyolysis, and vision loss. Progressive peripheral neuropathy is an irreversible complication. We report a unique case of a 5-year-old boy with slowly worsening limb weakness. Genetic analysis revealed a novel homozygous HADHA mutation causing his MTP deficiency, representing the first described occurrence in India. Exome sequencing comprehensively analyzed genes. The patient exhibited sensorimotor axonal neuropathy with secondary muscle atrophy, reflecting neuromyopathy. Our study provides further insight into genotype-phenotype correlations in mitochondrial trifunctional protein deficiency.