A research group at Kyoto University announced that it has discovered a new hereditary aplastic anemia that has been overlooked, "ADH5 / ALDH2 deficiency."
Hereditary aplastic anemia is a serious and intractable disease in children, and it often progresses to leukemia. Therefore, its elucidation is an important research subject in medicine and life science.The most typical and most frequent is "Fanconi anemia", which cannot repair damaged DNA, but this time, the results of genome analysis of the samples of patients with aplastic anemia of unknown cause collected so far using a next-generation sequencer. , Fanconi Anemia-like symptoms have been discovered in a completely new disease.
A patient with this disease was found to have mutations in both the ADH5 gene and the ALDH2 gene, making it the first example of inborn errors of regenerative anemia caused by intracellular metabolic disorders. ADH5 is a degrading enzyme gene for formaldehyde (= formalin), a toxic substance that damages biomolecules such as DNA in the body, and ALDH2 is a degrading enzyme gene for acetaldehyde produced in the body from alcohol. ALDH2 was well known as a gene that determines whether alcohol can be drunk or not, but this time, it was found that it is also important for the decomposition of formalin. Patients with ADH5 / ALDH2 deficiency are said to be unable to degrade formalin, which is naturally produced in the body, resulting in accumulation of genomic damage and aplastic anemia.
People who have a red face after drinking alcohol are considered to have the ALDH2 mutation, and the ALDH2 mutation itself is not unusual in as many as 50% of East Asians, including Japanese. No.This result is also significant in that we have found that mutations possessed by a large number of people are part of the cause of rare diseases.
This discovery will enable patients who were previously undiagnosable to be diagnosed, and is expected to lead to more accurate treatment. In the future, research on treatment methods using iPS cells created from patients will be promoted.
Paper information:[Molecular Cell] Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans
