Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. Stroke-like episodes, which are usually transient and not-disabling, represent the clinical hallmarks. Additional features include seizures, cognitive decline, psychosis, lactic acidosis, migraine, visual impairment, hearing loss, short stature, diabetes and myopathy. MRI shows hyperintensities on T2-weighted and DWI sequences mostly over the temporal, parietal and occipital regions, not confined to a vascular territory. Muscle biopsy typically shows ragged-red and COX-negative fibers, SDH hyperreactivity and, at ultrastructural level, abnormally shaped mitochondria with paracristalline inclusions. MELAS results in 80% of cases from a point mutation, m.3243A>G in the mitochondrial tRNA
Leu(UUR) gene (MTTL1) [
1,
2]. Other mitochondrial DNA (mtDNA) mutations in
MTTL1 gene and other transfer RNA genes (
MTTF,
MTTV,
MTTQ) as well as mutations in other subunits of complex 1 such as MTND1, MTND5 and MTND6 have been also identified as cause of MELAS [
3‐
6]. Indeed, mutations in nuclear genes leading to secondary mtDNA changes (depletions and multiple deletions), have been described as emerging causes of MELAS [
7]. Recently, Deschauer et al. described a patient showing stroke-like episodes and a right occipital lesion, headache, seizures, elevated CSF lactate, ragged–red fibers and carrying heterozygous mutations in mtDNA polymerase gene (
POLG1) arguing that MELAS could be included in
POLG1 spectrum phenotype [
7].
POLG1 mutations were described, so far, in families with autosomal dominant and recessive chronic progressive external ophthalmoplegia (PEO), Alpers syndrome, parkinsonism, optic neuritis and late onset ataxia [
8,
9]. We previously reported a cohort of 67 patients affected by myopathy with or without PEO, in which 19.4% of patients carried
POLG1 mutations [
10]. Herein, we report the 2-year neurological follow up of one of these patients disclosing over time a clinical phenotype highly consistent with MELAS.