The investigation, led by researchers from Massachusetts General Hospital (MGH) and Children’s Hospital Philadelphia (CHOP), has identified mitochondrial disease in a set of identical twins that had not previously been reported.
Diseases that affect the mitochondria-specific compartments within cells that contain their DNA and convert the food we eat into the energy needed to sustain life usually interfere with mitochondrial function, but these two In typical patients, mitochondria were overactive.
So, as reported in the New England Journal of Medicine, even though the siblings were consuming more calories than they needed, they had a very low body weight. “This is a very unusual mitochondrial phenotype. There are over 300 rare genetic mitochondrial diseases, and almost all of them are associated with blockage of mitochondria,” said senior author Vamsi K. Mutha, MD, professor of systems biology and medicine. in MGH.
Genome sequencing revealed a mutation in an enzyme called mitochondrial ATP synthase, which is required by cells to generate the energy storage molecule ATP. Experiments indicated that this mutation creates “leaky” mitochondria that dissipate energy—a process known as mitochondrial uncoupling.
“We propose a new name, mitochondrial uncoupling syndrome—which presents with hyper metabolism and uncoupling mitochondria,” says Mutha. These cases are of great importance for the fields of rare disease genetics, mitochondrial biology and metabolism.
The authors note that additional studies on mitochondrial uncoupling syndrome may provide insight into differences in energy metabolism in the general population.
Rebecca D., an attending physician in the Mitochondrial Medicine Program at CHOP and co-author of the study. “These twins represent the first disorder of mitochondrial uncoupling where we have been able to find a genetic cause,” Ganetzky said.
He adds, “From the discovery of pathogenic variants in ATP synthase that can cause mitochondrial uncoupling, these twins may be the first identified patients in the entire class of diseases of mitochondrial coupling.”