This is a neurodegenerative condition that is evident in infancy or in rare cases, it can occur among the teenage or adults. Leigh disease presents the progressive loss of mental and movement abilities of the affected individuals who often die within few years from the respiratory failure. It is estimated that around 1 in 40,000 infants are affected with Leigh disease.
Causes
Around 75 genetic mutations are identified to cause this disease. While most cases are related to the mutation in the nuclear DNA, around 20 percent develops as the result of the mutation in mitochondrial DNA. Most of the genes related to this syndrome are necessary for the production of energy in the mitochondria which uses oxygen to convert energy from food through the process known as oxidative phosphorylation. Five different protein complexes are involved in this process and are named as complex I, complex II, complex III, complex IV and complex V. The genetic mutation can affect the proteins in these complexes or their assembly may be disrupted. Around one-third of these cases is the result of disruption of complex I. It is believed that the impaired oxidative phosphorylation can cause the cell death from decreased energy in the cell. The cell death in the brain and other sensitive tissues contributes to the features associated with this disease. The inheritance in most cases is autosomal recessive manner meaning both copies of the gene in each cell have the mutation. In around 20% of the cases, the inheritance is a mitochondrial pattern, also known as maternal inheritance. As only the egg cells can pass the mitochondria to the children, mtDNA mutations are inherited from the mother only. In few of the cases, the inheritance pattern is X-linked recessive which usually occurs in males as they only inherit one X chromosome.
Symptoms
The symptoms vary greatly between the affected cases. The initial sign is diarrhea, vomiting and difficulty with swallowing that causes a problem with normal growth and gaining weight. They can also exhibit severe muscle and movement problems, weak muscle tone (hypotonia), loss of sensation, weakness of the limbs (peripheral neuropathy) and involuntary muscle contractions (dystonia). In addition, they may also present paralysis of the muscles that move the eyes (ophthalmoparesis), involuntary movement of the eye (nystagmus) and acute respiratory failure from severe breathing problems.
Diagnosis
The diagnosis is possible with the MRI or CT scan of the brain which can detect the abnormal sections. The small or large cysts may also be evident in the cerebral cortex of the brain. In the laboratory tests, the blood sample can reveal high levels of acidic waste substances and alanine. Some of the children may have deficiencies of the enzymes pyruvate dehydrogenase complex or cytochrome C oxidase.
Treatment
The treatment is based on the specific symptoms evident in each of the affected individual. One of the common treatments is the administration of thiamine or thiamine derivatives. Individuals with the deficiency of pyruvate dehydrogenase enzyme complex, a low carbohydrate and high-fat diet may be beneficial. The affected cases should be regularly monitored for evaluations with specialists. Genetic counseling may be beneficial for the affected individuals and their families.
References
https://rarediseases.info.nih.gov/diseases/6877/disease
https://rarediseases.org/rare-diseases/leigh-syndrome/
https://ghr.nlm.nih.gov/condition/leigh-syndrome#inheritance
