CHOP Researchers Find That Differences in Mitochondria Lead to More Severe Cases of Rare Genetic Disease

Even when patients share the same genetic disease, their clinical presentation can vary widely, an indication that there must be some underlying factors causing these differences. In one particular genetic disease, differences in mitochondria – the energy sources for cells – may solve the mystery of clinical variability.

Xilma R. Ortiz-Gonzalez, MD, PhD In a new study published in the journal Brain Communications, researchers from Children’s Hospital of Philadelphia (CHOP) examined whether mitochondrial function and mitophagy – a sort of “trash collection” system that recycles used up materials in cells – were altered in the TBCK gene in patients with neurological impairment caused by variants of that gene. The study found that mitochondrial dysfunction was more pronounced in cell lines derived from patients with more severe disease.

“There was nothing intrinsically wrong with the mitochondria we saw, but the bad mitochondria was not being properly recycled through mitophagy and appeared to be accumulating in patients with worse disease,” said senior author Xilma Ortiz-Gonzalez, MD, PhD, a pediatric neurologist in the Division of Neurology at CHOP.

Ortiz-Gonzalez explained that in these patients, lysosomes are not functioning properly, and they are critical in recycling cellular waste as part of mitophagy. This may represent a valuable target, but more research is needed.