Atypical Leigh syndrome associated with the D393N mutation in the mitochondrial ND5 subunit

Abstract

Leigh syndrome (LS) is a neurodegenerative disorder usually starting before 1 year of age and leading to death within months or years.1 In most patients, LS is caused by defects of mitochondrial oxidative phosphorylation (OXPHOS), the most common involving pyruvate dehydrogenase complex (PDH), cytochrome c oxidase (complex IV), and NADH-ubiquinone oxidoreductase (complex I).1 Complex I consists of at least 45 subunits,2 7 of which are encoded by the mitochondrial genome, and is the largest and the most complex in terms of function and structure among the OXPHOS complexes. Recent focus on the culprit role of nuclear genes encoding the majority of the structural subunits of complex I was the effect of the discovery of autosomal recessive mutations in several patients with LS or Leigh-like phenotypes. More recently, the 12706T>C and the 13513G>A mutations in the ND5 gene, one of seven subunits of complex I encoded by mitochondrial genome (mtDNA), were identified in patients with LS.3,4⇓ Thus, both nuclear gene defects and mtDNA mutations are possible in patients with LS with complex I deficiency. Here we report on an additional child with LS harboring the 13513G→A mutation. A 4-year-old Italian boy, born to unrelated parents, was the product of uncomplicated pregnancy and delivery. He …