Mitochondrial DNA depletion hepatocerebral Mpv17 related syndrome ..., (Mpv17-related mitochondrial DNA depletion syndrome hepatocerebral) - Gen Mpv17            

Syndrome hepatocerebral mitochondrial DNA depletion related to Mpv17, is a hereditary process that can lead to liver disease and neurological problems. Signs and symptoms of this disease start in childhood and usually include vomiting, diarrhea and growth retardation. Many affected infants have lactic acidosis and hypoglycemia. During the first weeks of life, newborns develop liver disease progresses rapidly to liver failure, characterized by hepatomegaly and cholestasis. Rarely, affected children develop liver cancer. After the onset of liver disease, many affected children develop neurological problems that can include developmental delay, hypotonia and peripheral neuropathy. Individuals with mitochondrial DNA depletion hepatocerebral related to Mpv17 syndrome usually only survive in infancy or early childhood.

This syndrome is most often seen in the population of Indians Navajos in the Southwest of the United States. In this population, the disease is known as Navajo neurohepatopatía type. These individuals typically have a life expectancy longer than people with mitochondrial DNA depletion hepatocerebral Mpv17 related syndrome. In addition to the signs and symptoms described above, people with type neurohepatopatía Navajo may have insensitivity to pain, which can lead to bone fractures painless and self - mutilation of fingers and toes. These people may lack sensitivity in the cornea, which can cause ulcers and scarring of the cornea, leading to vision problems. The cause of these additional features is unknown.

This process is due to alterations in the gene sequence Mpv17 (Mpv17, mitochondrial membrane protein inner), located on the short arm of chromosome 2 (2p23.3), which encodes a protein whose function is largely unknown. The Mpv17 protein is found in the inner membrane of mitochondria. Mitochondria participate in a wide variety of cellular activities, including energy production, chemical signaling, and the regulation of growth and cell division. Mpv17 is likely that the protein is involved in the maintenance of mtDNA. Having an adequate amount of mtDNA is essential for normal energy production within cells.

We found more than 30 mutations in the gene in Mpv17 people with mitochondrial DNA depletion hepatocerebral syndrome. A mutation that almost exclusively affects the population of the Navajos Indians Southwestern United States replaced the amino acid arginine by the amino acid glutamine at position 50 of the protein (R50Q). This mutation results in the synthesis of an unstable protein Mpv17 rapidly decomposes. Changes in Mpv17 protein including the R50Q mutation impair protein function and reduce the amount of protein that is available. A Mpv17 dysfunctional or absent protein causes problems with maintaining mtDNA, which can lead to a decrease in mitochondrial DNA. The decline in mitochondrial DNA altered mitochondrial function in many tissues of the body, particularly the brain, liver and other tissues that have high energy requirements and cells. The reduced mitochondrial function in the liver and brain leads to liver failure and neurological dysfunction associated with the syndrome. Studies indicate that the less mtDNA is available in cells, more intense are the manifestations of the disease.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome hepatocerebral mitochondrial DNA depletion related Mpv17 by the complete PCR amplification of exons Mpv17 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).