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A 6-year-old boy comes to the office because his parents have noticed that he is unable to keep up with his friends at the playground. He tires easily and points to his thighs when asked if anything hurts him. He has a history of myoclonic epilepsy. A muscle biopsy is performed and shows ragged red muscle fibers. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
These mitochondria are unable to generate adenosine triphosphate, or ATP, which is a form of energy used by our cells.
As a result, muscle cells, which require a lot of energy to function, stop functioning properly.
The mitochondria are the main energy producing factories of a cell, and they do so with the help of the electron transport chain, and the enzyme ATP synthase.
The electron transport chain is made up of complexes of proteins or lipids, called electron carriers, embedded within the inner mitochondrial membrane which pass electrons along like the baton in a relay race.
This movement of electrons helps establish a proton gradient that drives ATP synthase to phosphorylate adenosine diphosphate or ADP into ATP.
Primary mitochondrial myopathy is caused by a mutation either in the mitochondrial DNA or nuclear DNA, which results in the abnormal production of mitochondrial proteins, impairing the function of the electron transport chain.
Mutations in the nuclear DNA are commonly inherited in an autosomal dominant fashion, which means one mutated gene is enough to cause the disease; or autosomal recessive fashion, which means two mutated genes, one from each parent, are needed to cause the disease.
Mutations in the mitochondrial DNA follow maternal inheritance , meaning that only an affected woman can pass on the disease to her children.
This is because, typically during fertilization, the father's mitochondria are left behind while the sperm’s nucleus alone enters the egg.
The exception is the mitochondrial DNA single deletion, a common cause of primary mitochondrial myopathy, which is always sporadic and cannot be transmitted to the offspring.
In primary mitochondrial myopathy, muscle cells are unable to generate ATP, which results in muscle weakness and fatigue.
Sometimes there may also be muscle pain, cramping, stiffness, or even paralysis of the muscle.
Individuals typically develop exercise intolerance, which is a reduced ability to perform physical activity.
Symptoms vary based on the group of muscles affected.
In most individuals, the first to be affected are the extraocular muscles which control eye movements, which results in progressive external ophthalmoplegia.
- "Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy" Neurology (2018)