Hypochromic microcytic anemia with iron overload (hypochromic microcytic anemia with iron overload) - SLC11A2 gene.

Hypochromic microcytic anemia with iron overload is a disease that affects the normal transport of iron into cells. In this disease, the erythrocytes can not access the blood iron anemia prococando is evident from birth. Which is usually red cells are microcytic and hypochromic. The disease is manifested by pallor, fatigue and slow growth.

Microcytic hypochromic anemia in iron overload, the iron is not used by erythrocytes accumulates in the liver, and can eventually impair its function. Liver problems usually manifest themselves in adolescence or early adulthood.

This process is due to mutations in SLC11A2 gene will, located on the long arm of chromosome 12 (12q13). This gene encodes a protein called divalent metal transporter 1 of (T1DM). Four DMT1 protein isoforms are encoded from SLC11A2 gene. Each isoform is specific for one or more tissues, but some form of T1DM protein is found in all tissues. The main function of the DMT1 protein is to transport iron ions into the cells. This protein can also carry other metal ions. In the duodenum, the DMT1 protein is inside the microvilli. These projections absorb nutrients from food as it passes through the intestine and subsequently released into the bloodstream. In other cells, including erythroblasts, DMT1 is located in the membrane of endosomes, where transports iron to the cytoplasm so that it can be used by the cell.

They have been described at least seven mutations in the SLC11A2 gene leading to microcytic hypochromic anemia with iron overload. Most of these genetic changes replaced amino acids in the DMT1 protein. These mutations reduce the DMT1 protein synthesis, decrease protein function or impair the ability of the protein to achieve the correct location in cells. In erythroblasts, DMT1 protein deficiency decreases the amount of iron transported into the cells. As a result, the development of healthy red blood cells deteriorates, resulting in a deficiency of these cells. In the duodenum, DMT1 protein deficiency decreases iron absorption. To compensate for this decrease, the cells increase the functional protein coding DMT1, increasing iron absorption. Because erythrocytes can not use iron absorbed, it accumulates in the liver, possibly by altering liver function. Lack of iron in erythrocytes and iron accumulation in the liver causes the signs and symptoms of hypochromic microcytic anemia with iron overload.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform mutation detection microcytic hypochromic anemia associated with iron overload, by complete PCR amplification of exons SLC11A2 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).