MELAS syndrome: correlation between clinical features and molecular genetic analysis

The clinical manifestations and mitochondrial DNA (mtDNA) mutations in a Taiwanese family with a female proband exhibiting mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes syndrome are reported. Clinically, the proband had a stroke‐like episode with right hemiparesis, hemianopsia and mental dysfunction as well as short stature, hearing impairments, and elevated lactate levels. Brain magnetic resonance images showed multiple increased signal intensities over the left frontal, parietal and temporal areas. There were no ragged‐red fibers, but paracrystalline inclusion bodies were shown in the muscle biopsies under electron microscopic examination. A deficiency of NADH‐CoQ reductase was also found in biochemical studies of the muscles. The family survey revealed no abnormal findings except for headache and episodic vomiting in her mother. The molecular analysis of mtDNA disclosed a mutation from A to G at the nucleotide pair 3243 of the mitochondrial transfer RNA^Leu gene in the blood, hair follicles and/or muscle of the maternal relatives. A characteristic finding of the MELAS family is variation of percentage of mutated mtDNA in various tissues and individuals. However, a higher proportion of mutated mtDNA was noted in the proband than that in the asymptomatic or oligosymptomatic family members. From the data, the variable clinical phenotypes in this MELAS family can be explained at least partly, by the different proportions of mutant mtDNA in the target tissues of the profound and maternal relatives.