ORPHA: 83642; DO: 0050642;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.12 | Anemia, hypochromic microcytic, with iron overload 1 | 206100 | Autosomal recessive | 3 | SLC11A2 | 600523 |
A number sign (#) is used with this entry because of evidence that hypochromic microcytic anemia with iron overload-1 (AHMIO1) is caused by homozygous or compound heterozygous mutation in the SLC11A2 gene (600523) on chromosome 12q13.
Another form of hypochromic microcytic anemia with iron overload (AHMIO2; 615234) is caused by mutation in the STEAP3 gene (609671) on chromosome 2q14.
Shahidi et al. (1964) described hypochromic microcytic anemia in a brother and sister of French-Canadian extraction. An error in iron metabolism was characterized by high serum iron, massive hepatic iron deposition, and absence of stainable bone marrow iron stores. No defect in transferrin or in the qualitative aspects of heme synthesis could be shown. The parents and 2 other sibs were normal. Despite adequate transferrin-iron complex, delivery of iron to the erythroid bone marrow was apparently insufficient for the demands of hemoglobin synthesis.
Mims et al. (2005) reported a patient with severe hypochromic microcytic anemia and iron overload who had previously been reported by Priwitzerova et al. (2004) as having a defect in iron transport and utilization in erythroid cells. The patient was the offspring of a consanguineous union and came to medical attention at the age of 3 months because of severe hypochromic microcytic anemia. Bone marrow examination showed erythroid hyperplasia with features of abnormal erythroid maturation; reticulocyte count was normal to slightly elevated. Serum iron levels were consistently elevated, ferritin levels were normal to slightly increased, and serum transferrin receptor levels were greatly increased. The patient received, on average, one transfusion per year, but her development was unremarkable with no obvious organ dysfunction. At the age of 8 years, she developed mild liver function abnormalities, and liver biopsy at age 19 demonstrated significantly increased iron deposition in both Kupffer cells and hepatocytes, despite the fact that the volume of transfusions she had received was not sufficient for development of hepatic hemosiderosis.
Iolascon et al. (2006) reported a 5-year-old boy, born of nonconsanguineous southern Italian parents, with hypochromic microcytic anemia and severe hepatic iron overload. A striking reduction of the resulting protein in peripheral blood mononuclear cells was demonstrated by Western blot analysis. The boy required blood transfusions until adequate hemoglobin levels were achieved with erythropoietin treatments.
In a female patient with severe hypochromic microcytic anemia and iron overload in whom no mutations were identified in the TFR1 (TFRC; 190010) or FPN1 (SLC40A1; 604653) gene, Mims et al. (2005) identified homozygosity for a missense mutation in the SLC11A2 gene (600523.0001). This patient had previously been reported by Priwitzerova et al. (2004) as having a defect in iron transport and utilization in erythroid cells.
In a 5-year-old boy with hypochromic microcytic anemia and severe hepatic iron overload, Iolascon et al. (2006) identified compound heterozygosity for mutations in the SLC11A2 gene (600523.0002 and 600523.0003).
Beaumont et al. (2006) reported a 6-year-old French girl with hypochromic microcytic anemia and severe hepatic iron overload in whom they identified compound heterozygosity for a deletion (600523.0004) and a missense (600523.0005) mutation in the SLC11A2 gene. The unaffected father was heterozygous for the deletion, and the unaffected mother and sister were heterozygous for the missense mutation. Noting that their patient had less severe anemia than that of the 2 patients previously described by Priwitzerova et al. (2004) and Iolascon et al. (2006), respectively, Beaumont et al. (2006) suggested that the rather conservative G212V substitution might have retained some iron transport function. All 3 patients had hepatic iron overload associated with paradoxically normal to moderately elevated serum ferritin levels.
Beaumont, C., Delaunay, J., Hetet, G., Grandchamp, B., de Montalembert, M., Tchernia, G. Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood 107: 4168-4170, 2006. [PubMed: 16439678] [Full Text: https://doi.org/10.1182/blood-2005-10-4269]
Iolascon, A., d'Apolito, M., Servedio, V., Cimmino, F., Piga, A., Camaschella, C. Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2) (sic). Blood 107: 349-354, 2006. [PubMed: 16160008] [Full Text: https://doi.org/10.1182/blood-2005-06-2477]
Mims, M. P., Guan, Y., Pospisilova, D., Priwitzerova, M., Indrak, K., Ponka, P., Divoky, V., Prchal, J. T. Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood 105: 1337-1342, 2005. [PubMed: 15459009] [Full Text: https://doi.org/10.1182/blood-2004-07-2966]
Priwitzerova, M., Pospisilova, D., Prchal, J. T., Indrak, K., Hlobilkova, A., Mihal, V., Ponka, P., Divoky, V. Severe hypochromic microcytic anemia caused by a congenital defect of the iron transport pathway in erythroid cells. Blood 103: 3991-3992, 2004. [PubMed: 15121718] [Full Text: https://doi.org/10.1182/blood-2004-01-0225]
Shahidi, N. T., Nathan, D. G., Diamond, L. K. Iron deficiency anemia associated with an error of iron metabolism in two siblings. J. Clin. Invest. 43: 510-521, 1964. [PubMed: 14135503] [Full Text: https://doi.org/10.1172/JCI104937]