Normal neuroimaging in an infant with SUCLA2-related mitochondrial DNA depletion syndrome type 5: a case report of likely pathogenic variant

Abstract

Abstract Mitochondrial DNA depletion syndrome type 5 (MTDPS5), caused by SUCLA2 mutations, is a rare autosomal recessive disorder manifesting as early-onset encephalomyopathy. Clinical diagnosis is challenging due to phenotypic overlap and potentially unremarkable early investigations. We report a male infant of consanguineous parents who presented with progressive hypotonia, global developmental delay, and involuntary nocturnal movements at 3 months. Despite an unremarkable newborn metabolic screen and normal initial brain MRI, the patient demonstrated a significant failure to achieve age-appropriate gross motor milestones, including independent sitting and crawling, by 12 months. Whole-exome sequencing (WES) definitively identified a homozygous likely pathogenic SUCLA2 variant (p.Met329Val). Following the initiation of a mitochondrial cocktail, the patient showed substantial clinical improvement. This case emphasizes that MTDPS5 should be considered in infants with unexplained encephalomyopathy, even when initial findings are normal, underscoring the necessity of early WES to guide clinical management.