Proximal Myopathy With Focal Depletion Of Mitochondria

Clinical Features

Genge et al. (1995) described 2 sibs, a brother and sister, as well as a third unrelated female with severe myalgias after exercise. The asymptomatic father of the 2 sibs had an elevated creatine kinase level, suggesting autosomal dominant inheritance. Onset of symptoms began in adolescence. In the resting state, there was mild proximal weakness with creatine kinase activity in the range of 1,000 units per liter, rising to 10,000 units per liter after exercise. In the 2 sibs, phosphorylation potentials were low and recovery of phosphorylation potential was mildly delayed. Large areas of about one-third of type II fibers were completely devoid of mitochondria with the remaining mitochondria unusually large but otherwise normal. No depletion or rearrangement of mitochondrial DNA was observed. The focal lack of mitochondria seen histologically was different from that observed in the central core disease (117000) or in multicore myopathy (255320), or other general pathological changes such as target fibers of denervation, Z disc streaming, or motheaten fibers. They distinguished it also from the myopathic form of mtDNA depletion syndrome (see, e.g., MTDPS2, 609560). Genge et al. (1995) speculated that there may be an impairment of normal mitochondrial proliferation.