Fanconi anemia and Aldehyde Degradation Deficiency Syndrome: Metabolism and DNA repair protect the genome and hematopoiesis from endogenous DNA damage

• Published in: DNA repair Vol. 130; p. 103546
• Main Authors: Mu, Anfeng, Hira, Asuka, Mori, Minako, Okamoto, Yusuke, Takata, Minoru
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2023
• Subjects: ADH5; Aldehyde Degradation Deficiency Syndrome; ALDH2; Fanconi anemia; Formaldehyde; ALDH2; Fanconi anemia; Aldehyde Degradation Deficiency Syndrome; ADH5; Formaldehyde
• ISSN: 1568-7864; 1568-7856
• DOI: 10.1016/j.dnarep.2023.103546

We have identified a set of Japanese children with hypoplastic anemia caused by combined defects in aldehyde degrading enzymes ADH5 and ALDH2. Their clinical characteristics overlap with a hereditary DNA repair disorder, Fanconi anemia. Our discovery of this disorder, termed Aldehyde Degradation Deficiency Syndrome (ADDS), reinforces the notion that endogenously generated aldehydes exert genotoxic effects; thus, the coupled actions of metabolism and DNA repair are required to maintain proper hematopoiesis and health. •We discovered a novel disorder caused by combined defects in aldehyde degrading enzymes ADH5 and ALDH2.•This disorder is clinically Fanconi anemia-like and now termed Aldehyde Degradation Deficiency Syndrome (ADDS).•We concluded that the coupled actions of metabolism and DNA repair are required to maintain proper hematopoiesis and health.