Scientists affiliated with Massachusetts General Hospital (MGH) and Children’s Hospital Philadelphia recently identified a novel mitochondrial disorder in a pair of identical twins. Doctors began studying these twins when they presented with unique symptoms. Despite higher caloric intake, neither twin seemed to gain much – if any – weight. Rather, the twins had low overall body weight.
According to an article on MSN, initially published on Boston.com, scientists dove into research. Through initial research, the scientists identified mitochondria (and mitochondrial dysfunction) as the driving force behind the twins’ condition. The National Human Genome Research Institute defines mitochondria as:
membrane-bound cell organelles (mitochondrion, singular) that generate most of the chemical energy needed to power the cell’s biochemical reactions. Chemical energy produced by the mitochondria is stored in a small molecule called adenosine triphosphate (ATP).
In this case, the research team performed whole exome sequencing on the twins. They found that the mitochondrial ATP synthase enzyme, which helps generate ATP, was mutated. More so, the twins’ mitochondria were high-functioning and very active. This is a stark difference from many mitochondrial diseases in which the mitochondria do not function effectively. Thus, between the mutation and the high activity, the twins’ bodies were using energy in a way that prevented them from gaining weight.
Naming a Novel Disorder: Mitochondrial Uncoupling Syndrome
More so, the research team found that the mitochondrial ATP synthase mutation led to mitochondrial uncoupling. As explained by an unrelated 2019 research article published in Cells:
Mitochondrial uncoupling can be defined as a dissociation between mitochondrial membrane potential generation and its use for mitochondria-dependent ATP synthesis. A severe mitochondrial uncoupling can lead to rapid cellular ATP depletion and, if the stress persists, to the triggering of other cellular mechanisms, such as cell death.
In more basic terms, mitochondrial uncoupling leads to mitochondria that “leak” energy rather than keep it. Currently, the research team has proposed that this novel condition be called mitochondrial uncoupling syndrome. For now, the main symptoms and characteristics are uncoupled mitochondria and hypermetabolism.
This is the first time that mitochondrial uncoupling syndrome has been reported or described in medical literature. Moving forward, more research is needed to better understand this condition – and how many other potential patients there might be.
