Clinical and genetic characteristics of congenital sideroblastic anemia: comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS)

Abstract

Sideroblastic anemia is characterized by anemia with the emergence of ring sideroblasts in the bone marrow. There are two forms of sideroblastic anemia, i.e., congenital sideroblastic anemia (CSA) and acquired sideroblastic anemia. In order to clarify the pathophysiology of sideroblastic anemia, a nationwide survey consisting of clinical and molecular genetic analysis was performed in Japan. As of January 31, 2012, data of 137 cases of sideroblastic anemia, including 72 cases of myelodysplastic syndrome (MDS)–refractory cytopenia with multilineage dysplasia (RCMD), 47 cases of MDS–refractory anemia with ring sideroblasts (RARS), and 18 cases of CSA, have been collected. Hemoglobin and MCV level in CSA are significantly lower than those of MDS, whereas serum iron level in CSA is significantly higher than those of MDS. Of 14 CSA for which DNA was available for genetic analysis, 10 cases were diagnosed as X-linked sideroblastic anemia due to ALAS2 gene mutation. The mutation of SF3B1 gene, which was frequently mutated in MDS-RS, was not detected in CSA patients. Together with the difference of clinical data, it is suggested that genetic background, which is responsible for the development of CSA, is different from that of MDS-RS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-012-1564-5) contains supplementary material, which is available to authorized users.

Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia

“…1 It has been reported that the human ALAS2 gene is mapped on the X chromosome, 2 and that a loss-of-function mutation of this gene causes X-linked sideroblastic anemia (XLSA), 3,4 which is the most common genetic form of congenital sideroblastic anemia (CSA). Moreover, a missense mutation of ALAS2 was identified in a patient with non-familial CSA (nfCSA), 5 in which no family history of sideroblastic anemia was identified.…”

Microcytic anemia in a pregnant woman: beyond iron deficiency

“…In congenital sideroblastic anemia (CSA), Hb and MCV are usually lower than those of refractory anemia with ring sideroblasts (RARS) and refractory cytopenia with multilineage dysplasia (RCMD) cases; serum iron level in CSA is also commonly higher than that in RARS or RCMD [1,2]. This together with the presence of family history and the young age of the patient and the presence in the blood smear of a dimorphic population of red blood cells and a normal karyotype led us to apply genetic study of deltaaminolevulinate synthase 2 (ALAS2) gene.…”

“…The three most common causes of microcytosis are iron deficiency, the anemia of (chronic) inflammation, and alpha or beta thalassemia trait [1]. However, less frequent causes such as sideroblastic anemias, hemoglobinopathies, lead poisoning and rare and atypical inherited microcytic anemias due to defects of iron metabolism should be taken into account [2].…”

Iron metabolism in erythroid cells and patients with congenital sideroblastic anemia

“…Within these heme biosynthetic enzymes, the mutation of the ALAS2 gene is most frequently identified in patients with congenital sideroblastic anemia [49,50]. Since human ALAS2 gene is mapped to X chromosome [30,51], congenital sideroblastic anemia (CSA) caused by the mutation of ALAS2 gene exhibits X-linked inheritance pattern (X-linked sideroblastic anemia; XLSA).…”