Sweeney et al. (1993) reported a family exhibiting maternal inheritance of a variable syndrome comprising ocular, neck, and proximal upper limb weakness, psychiatric features, and sudden death. Of 15 definitely or probably affected individuals, 7 had died in early adult life, probably of respiratory failure. All living affected members of the family showed an A-to-G transition at nucleotide 3251 of the MTTL1 gene.
In a girl who died at age 14 from a rapidly progressive mitochondrial myopathy, Houshmand et al. (1996) found heteroplasmy for the A3251G mutation. A large proportion of muscle fibers contained accumulations of abnormal mitochondria but no cytochrome c oxidase deficient fibers were present. Studies of isolated muscle mitochondria revealed a profound isolated complex I deficiency. A high percentage of mutant mtDNA was found in muscle (94%), fibroblasts (93%), brain (90%), liver (80%), and heart (79%). The family was not available for investigation. The proportion of mutant mtDNA was 28% in normal-appearing fibers and 61% in abnormal fibers. The patient had been healthy until age 10 years when she had insidious onset of gastrointestinal symptoms with diarrhea, nausea, fatigue, and tachycardia on mild physical exertion. Terminally, in the last years of life she developed persistent tachycardia, lactic acidosis, and hypercapnia, and in the last month of life, cardiorespiratory failure.
