Question

What three criteria must a human disorder fulfill to be classified as a hereditary mitochondrial disease?

Short answer

Answer: A hereditary mitochondrial disease must meet the following criteria: 1) have a genetic basis in mitochondrial DNA, 2) lead to impaired mitochondrial function, and 3) present specific clinical manifestations or symptoms.

Step-by-step solution

1. Genetic Basis in Mitochondrial DNA

In order for a disorder to be classified as a hereditary mitochondrial disease, it must have a genetic origin in the mitochondrial DNA. This means that the disorder should result from a mutation, deletion, or duplication in the mitochondrial DNA, which is inherited from the mother since mitochondrial DNA is maternally inherited.

2. Impaired Mitochondrial Function

The disorder must directly affect the function of the mitochondria, either by impairing the generation of cellular energy (ATP) through oxidative phosphorylation or by disrupting other critical biochemical processes within the mitochondria. Proper mitochondrial function, including the generation of cellular energy and the maintenance of cellular health, is essential for normal cell function. A hereditary mitochondrial disease will directly or indirectly impair these processes leading to the disorder's symptoms.

3. Clinical Manifestations

Finally, a hereditary mitochondrial disease must be associated with specific clinical manifestations or symptoms. These symptoms are often caused by dysfunction or failure in cells or tissues that have high energy demands and thus are most affected by mitochondrial dysfunction. Examples of common clinical manifestations of mitochondrial disorders include muscle weakness, neurodegeneration, cardiomyopathies, and multisystem involvement.