AMeD syndrome is characterized by aplastic anemia, mental retardation, short stature, and microcephaly and is caused by digenic mutations in the aldehyde dehydrogenase 2 ( ALDH2) and alcohol dehydrogenase 5 ( ADH5) genes. We have successfully performed hematopoietic stem cell transplantation in two patients with AMeD syndrome and isochromosome 1q. AMeD syndrome with myelodysplastic syndrome or acute myeloblastic leukemia generally has a poor prognosis; however, early diagnosis may improve treatment response. Although the gain of 1q has been considered as a form of early clonal evolution in Fanconi anemia, it may be an equally important finding observed in AMeD syndrome.