Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia. Classical anemia is a normochromic or macrocytic anemia with reticulocytopenia. Patients with DBA are usually diagnosed and receive transfusion in the first year. We report a patient who presented with microcytic anemia and congenital malformations. The patient suffered a sudden aggravation of disease during adolescence and received first transfusion at 13 years of age. Exome sequencing eventually led to a diagnosis of DBA with a mutated RPL5 gene. In conclusion, this case demonstrates a confused manifestation of non-classical DBA and sudden aggravation of disease in natural course of DBA.