Anemia, Sideroblastic, 2, Pyridoxine-Refractory

A number sign (#) is used with this entry because of evidence that sideroblastic anemia-2 (SIDBA2), which is refractory to pyridoxine treatment, is caused by homozygous or compound heterozygous mutation in the SLC25A38 gene (610819) on chromosome 3p22.

For a discussion of genetic heterogeneity of sideroblastic anemia, see SIDBA1 (300751).

See 206000 for a possible pyridoxine-responsive form of autosomal sideroblastic anemia.

Clinical Features

Manabe et al. (1982) reported a female Japanese infant who was pale from birth and was found to have marked microcytic hypochromic anemia with 29 ringed sideroblasts per 100 nucleated cells in the bone marrow. The M:E ratio was 0.35 and the total sideroblast count was 89%. Delta-aminolevulinic acid synthetase (ALAS2; 301300) was very low in erythroblasts of this patient. The addition of pyridoxal phosphate had no clinical benefit. The mother had an intermediate level of the enzyme. The father could not be studied, but the authors suspected that both parents were heterozygous, consistent with possible autosomal recessive inheritance.

Jardine et al. (1994) reported a brother and sister with transfusion-dependent, pyridoxine-refractory sideroblastic anemia from birth. Clinical features included microcytic, hypochromic anemia and hepatosplenomegaly. Genetic studies excluded linkage to and mutation in the ALAS2 gene, thus excluding the more common X-linked form of the disorder (SIDBA1; 300751). Inheritance was postulated to be autosomal recessive.

Guernsey et al. (2009) reported 18 patients with autosomal recessive pyridoxine-refractory sideroblastic anemia. Most patients had onset in infancy of severe microcytic anemia and increased serum ferritin. Bone marrow aspirate showed ringed sideroblasts. The phenotype was similar to that seen in X-linked sideroblastic anemia.

Molecular Genetics

In 18 patients with autosomal recessive pyridoxine-refractory sideroblastic anemia, Guernsey et al. (2009) identified 11 different homozygous or compound heterozygous mutations in the SLC25A38 gene (see, e.g., 610819.0001-610819.0005). Three unrelated patients who were of Acadian descent from the Maritime Canadian provinces carried the same mutation (R117X; 610819.0001). The other patients were of northern European, Greek, Hispanic, and Asian Indian descent.