MT-TH

A small number of people with the features of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) have a mutation in the MT-TH gene. This condition is characterized by recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes including a loss of consciousness, seizures, and other problems affecting the nervous system. Some people with an MT-TH gene mutation also have features of another mitochondrial disorder called myoclonic epilepsy with ragged-red fibers (MERRF); these additional features can include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known as ragged-red fibers. This combination of signs and symptoms is called MERRF/MELAS overlap syndrome.

MT-TH gene mutations that cause MELAS and MERRF/MELAS overlap syndrome change single DNA building blocks (nucleotides) in the gene. Researchers have not determined how these genetic changes alter energy production in mitochondria or cause the varied signs and symptoms of MELAS or MERRF/MELAS overlap syndrome.

As mentioned above, a few individuals with a mutation in the MT-TH gene have features of both myoclonic epilepsy with ragged-red fibers (MERRF) and MELAS. The mutation involved in this overlap syndrome replaces the nucleotide guanine with the nucleotide adenine at gene position 12147 (written as G12147A). It remains unknown why this mutation causes the overlapping features of MERRF and MELAS.

Another mutation in the MT-TH gene may increase the risk of developing a heart condition called cardiomyopathy. People with cardiomyopathy have a weakened heart muscle that is unable to pump blood effectively. A particular change in the MT-TH gene has been identified in several adults with cardiomyopathy, but without other common signs of mitochondrial disease such as neurological abnormalities. This mutation replaces the nucleotide guanine with the nucleotide adenine at gene position 12192 (written as G12192A). It is unclear why this alteration in mitochondrial DNA may increase a person's risk of developing heart problems without affecting other parts of the body.