Multiple mtDNA deletions with features of MNGIE

Two sisters developed gastrointestinal malabsorption with pain and unsteady gait due to polyneuropathy at age 15. Both had ophthalmoplegia, neurogenic EMG, and COX-negative muscle fibers. One patient had low muscle complex I-IV activity, multiple mtDNA deletions, and depletion, but no thymidine phosphorylase (TP) or dNT-2 gene mutations. TP activity and brain MRI were normal. The condition resembles mitochondrial neurogastrointestinal encephalomyopathy, except for the absence of leukoencephalopathy, and is likely caused by a nuclear DNA mutation that disrupts intergenomic signaling.