In a set of an identical twins, investigators led by researchers at Massachusetts General Hospital (MGH) and Kid’s Hospital Philadelphia (CHOP) have identified a mitochondrial disease not previously reported.
Diseases that affect mitochondria-;specialized compartments inside cells that contain their very own DNA and convert the food we eat into energy needed to sustain life-;typically interfere with mitochondrial function, but in these two patients, mitochondria were hyperactive.
So, as reported within the Recent England Journal of Medicine, regardless that the siblings were eating much more calories than needed, their body weights remained very low.
This can be a highly unusual mitochondrial phenotype. There are greater than 300 rare genetic mitochondrial diseases, and nearly all of them are related to an interruption of mitochondria.”
Vamsi K. Mootha, MD, Senior Writer, Professor of Systems Biology and Medicine at MGH
Genome sequencing revealed a mutation in an enzyme called the 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 called mitochondrial uncoupling.
“We propose a latest name-;mitochondrial uncoupling syndrome-;that presents with hypermetabolism and uncoupled mitochondria,” says Mootha. “These cases are very vital for the sector of rare disease genetics, mitochondrial biology, and metabolism.”
The authors note that additional studies on mitochondrial uncoupling syndromes may provide insights into differences in energy metabolism in the overall population.
“These twins represent the primary disorder of mitochondrial uncoupling where we’ve got been capable of find the genetic cause,” said Rebecca D. Ganetzky, MD, an attending physician in Mitochondrial Medicine program at CHOP and co-author of the study.
“By discovering that pathogenic variants within the ATP synthase itself may cause mitochondrial uncoupling, these twins stands out as the first identified patients in an entire class of diseases of mitochondrial coupling.”
Additional co-authors include Andrew L. Markhard, BA, Irene Yee, BS, Sheila Clever, MSc, Alan Cahill, PhD, Hardik Shah, MS, Zenon Grabarek, PhD, and Tsz-Leung To, PhD.
This work was supported by the National Institutes of Health and others.
Source:
Massachusetts General Hospital
Journal reference:
Ganetzky, R.D., et al. (2022) Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation. Recent England Journal of Medicine. doi.org/10.1056/NEJMoa2202949.