Pearson syndrome is caused by defects in the mitochondrial DNA (mtDNA), which lead to a failure in the mitochondria’s ability to produce energy properly. Mitochondria are tiny structures inside cells that act like power plants, generating the energy cells need to function. When these mitochondria have damaged or missing pieces of their DNA, they cannot make enough energy, which causes cells and organs to malfunction. This energy shortage is especially harmful in organs that require a lot of energy, such as the bone marrow and pancreas, which are commonly affected in Pearson syndrome.
The root cause lies in deletions or mutations in the mitochondrial DNA. Unlike the DNA in the cell’s nucleus, mitochondrial DNA is inherited only from the mother and exists in multiple copies within each mitochondrion. In Pearson syndrome, large-scale deletions in this mitochondrial DNA disrupt the production of proteins essential for the mitochondria’s energy-generating machinery. Because mitochondria are responsible for producing most of the cell’s energy through a process called oxidative phosphorylation, any disruption in this process leads to widespread cellular energy deficiency.
This energy deficiency particularly impacts the bone marrow, where blood cells are produced, and the pancreas, which produces digestive enzymes and insulin. As a result, individuals with Pearson syndrome often experience severe anemia due to bone marrow failure and problems with digestion and blood sugar regulation due to pancreatic dysfunction.
The mitochondrial DNA deletions in Pearson syndrome usually occur spontaneously rather than being inherited from a parent. These deletions can vary in size and location but typically remove critical genes needed for mitochondrial function. Because mitochondria are present in nearly every cell, the effects of these deletions can be widespread, affecting multiple organ systems.
In addition to the direct loss of mitochondrial DNA segments, the defective mitochondria can cause increased production of harmful molecules called reactive oxygen species (ROS). These molecules can damage cellular components further, worsening the dysfunction. The body’s mechanisms to maintain mitochondrial quality and remove damaged mitochondria may become overwhelmed, leading to accumulation of dysfunctional mitochondria and further energy deficits.
Pearson syndrome is classified as a mitochondrial disease, a group of disorders caused by mitochondrial dysfunction. These diseases often affect multiple organs and systems because mitochondria are essential for energy production in all cells. The severity and range of symptoms depend on the extent of mitochondrial DNA damage and which tissues are most affected.
In summary, Pearson syndrome arises from large deletions in mitochondrial DNA that impair the mitochondria’s ability to generate energy. This energy failure primarily disrupts the function of the bone marrow and pancreas, leading to the characteristic symptoms of the syndrome. The mitochondrial DNA deletions usually occur spontaneously and cause widespread cellular energy deficits, which underlie the multisystem nature of the disease.
