OBJECTIVETo raise awareness of molecular pathogenesis and treatment of congenital sideroblastic anemia (CSA).

METHODSA complete blood count and iron metabolism were detected from the proband and other members of the family. Mutation analysis was performed on the complete coding regions of ALAS2 gene by common polymerase chain reaction (PCR) using genomic DNA as a template from members the family. ALAS2 mutations were detected by direct sequencing and mutation types were confirmed by sequencing followed by plasmid cloning.

RESULTSThe proband male presented with microcytic hypochromic anemia (hemoglobin 84 g/L, mean corpuscular volume 64 fL, mean corpuscular hemoglobin 16.5 pg), and iron overload (serum iron 44.7 μmol/L, serum ferritin 3 123 μg/L and transferrin saturation 0.84). A mutation 466 A>G predicting a Lys156Glu amino acid change was identified in the proband and 3 females from the family. The proband was hemizygous for this mutation and presented with microcytic anemia and iron overload, while all 3 heterozygous females showed marginally increased red cell distribution width without any other symptoms. The proband treated with 300 mg of pyridoxine per day and iron chelation therapy with deferoxamine for one year had durable hematopoietic patients improvements, including increase in hemoglobin to 98 g/L and decrease in serum ferritin to 1 580 μg/L.

CONCLUSIONThis was a novel K156E substitution in ALAS2 gene identified in a 3-generation pedigree in China. Our findings emphasized the importance of gene based diagnosis of CSA, and CSA patient with ALAS2 mutation responded to pyridoxine treatment.