Children Miocerebrohepatopatía, spectrum ... -MCHS- (Childhood myocerebrohepatopathy spectrum -MCHS-) - Gen Polg.
The spectrum of child miocerebrohepatopatía, commonly referred WSCM, it is part of a group of related disorders POLG. Alterations in this group have a number of similar signs and symptoms involving muscles, nerves and brain - related functions. WSCM usually becomes apparent in children a few months to 3 years old. Usually, people affected have problems with their muscles, brain and liver. Signs and symptoms of WSCM may include myopathy, developmental delay or impairment of intellectual function, liver disease, lactic acidosis and growth retardation. Other signs and symptoms may include WSCM renal tubular acidosis, pancreatitis, cyclic vomiting or hearing loss.
This process is due to mutations in the POLG gene, located on the long arm of chromosome 15 (15q25). This gene encodes the alpha subunit, gamma protein polymerase (pol ?). The alpha subunit, binds to two copies of the beta subunit to form pol ?. Pol ? is a DNA polymerase, which detects DNA sequences and used as targets for new DNA replication. These enzymes are important for replicating genetic material into cells. Polymerases also play a critical role in DNA repair. Pol ? is the only DNA polymerase is active in the mitochondria and can replicate mtDNA.
Most mutations in the POLG gene change individual amino acids in the alpha subunit of pol ?. These mutations reduce the activity of pol ?, which decreases the efficiency copy of mtDNA. As in other disorders related to the POLG gene, individuals with WSCM generally have mtDNA depletion in muscle, brain, or liver tissue. MtDNA depletion affects oxidative phosphorylation in these tissues and reduces the energy available to cells, which can lead to signs and symptoms of WSCM.
This disease is inherited in an autosomal recessive pattern, that is, 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 child miocerebrohepatopatía spectrum, by complete PCR amplification of the exons of the POLG 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).