A novel clinical phenotype of myopathy, sensorimotor neuropathy, infertility, and hypogonadism with multiple mitochondrial DNA deletions.

We describe a patient with myopathy, sensorimotor neuropathy, hypogonadism, and infertility with abnormal sperm mobility and morphology. Analysis of the deltoid muscle DNA revealed a G to A change at nt 1102 in the twinkle gene and multiple mitochondrial DNA deletions. Histochemistry revealed "ragged-red" fibers and many cytochrome-c oxidase negative fibers (32%) that lacked the mitochondrial encoded respiratory chain subunits I and II and the nuclear encoded subunit VIc. Respiratory chain enzyme analysis showed severe deficiency of complex I, III, and IV. This patient has no documented family history of progressive external ophthalmoplegia, which suggests either a sporadic or autosomal-recessive syndrome. This case is a novel phenotype for twinkle gene mutations and multiple mitochondrial DNA deletion syndromes, as these syndromes generally follow an autosomal-dominant inheritance pattern.