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 ... 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. Van Waveren Hogervorst et al. (1987) reported a large Dutch family with autosomal inheritance of erythrocyte dimorphism. Two family members, an 81-year-old woman and her 45-year-old son, had sideroblastic anemia. Pyridoxine treatment in the mother was ineffective. The authors suggested that the increased relative distribution width of red cells in this family, even in those without clinical anemia, represented autosomal 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 (XLSA; 300751). Inheritance was postulated to be autosomal recessive. Camaschella et al. (2007) reported a 60-year-old southern Italian man who presented with severe microcytic anemia, jaundice, hepatosplenomegaly, iron overload, and cirrhosis. Bone marrow showed moderate erythroid expansion and increased iron staining both in erythroblasts and macrophages, with 28% ringed sideroblasts. Folic acid and vitamin B6 supplementation was ineffective. Iron chelation therapy resulted in clinical improvement. Further analysis showed dysregulation of iron-regulatory proteins aconitase (ACO1; 100800) and IREB2 (147582). His unaffected parents were consanguineous, consistent with autosomal recessive inheritance. 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 (XLSA; 300751).
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 ... - SLC25A38 Gene 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. - GLRX5 Gene In a southern Italian man with autosomal recessive pyridoxine-refractory sideroblastic anemia, Camaschella et al. (2007) identified a homozygous mutation in the GLRX5 gene (609588.0001). The was considered to be the human counterpart of the zebrafish shiraz mutant, which shows a similar but more severe phenotype due to a deletion in the Glrx5 gene (Wingert et al., 2005).