Mitochondrial oxidative phosphorylation disorders in children: Phenotypic, genotypic and biochemical correlations in 85 patients from South India

- Eighty five children with mitochondrial OXPHOS disorders from India were studied.
- Isolated complex I deficiency was most common followed by multiple complexes, complex IV and complex III deficiencies.
- The most frequent neurological findings were ataxia and hypotonia followed by involuntary movements.
- Genetic analysis revealed variations in mitochondrial DNA, SURF1, and POLG1.
- This study highlights the wide range of phenotypes in children with OXPHOS disorders from India.

Mitochondrial oxidative phosphorylation (OXPHOS) disorders account for a variety of neuromuscular disorders in children. In this study mitochondrial respiratory chain enzymes were assayed in muscle tissue in a large cohort of children with varied neuromuscular presentations from June 2011 to December 2013. The biochemical enzyme deficiencies were correlated with the phenotypes, magnetic resonance imaging, histopathology and genetic findings to reach a final diagnosis. There were 85 children (mean age: 6.9 ± 4.7 years, M:F:2:1) with respiratory chain enzyme deficiency which included: isolated complex I (n = 50, 60%), multiple complexes (n = 24, 27%), complex IV (n = 8, 9%) and complex III deficiencies (n = 3, 4%). The most common neurological findings were ataxia (59%), hypotonia (59%) and involuntary movements (49%). A known mitochondrial syndrome was diagnosed in 27 (29%) and non-syndromic presentations in 57 (71%). Genetic analysis included complete sequencing of mitochondrial genome, SURF1, POLG1&2. It revealed variations in mitochondrial DNA (n = 8), SURF1 (n = 5), and POLG1 (n = 3). This study, the first of its kind from India, highlights the wide range of clinical and imaging phenotypes and genetic heterogeneity in children with mitochondrial oxidative phosphorylation disorders.