IllnessIron-refractory iron deficiency anemia, IRIDA; differential diagnosis

NGS +

[Sanger]

Iron-refractory iron deficiency anemia results from low blood iron levels. It is iron-refractory because completely resistant to oral and at least partially also resistant to intravenous iron administration. This anemia is hypochromic and microcytic. Symptoms include fatigue, weakness and skin pallor. The symptoms are more pronounced in childhood, but are usually mild. Children usually show normal growth and development. Mutations in the TMPRSS6 gene cause this autosomal recessive anemia. In another form of hypochromic microcytic anemia, the normal iron transport in the cells is impaired, leading to iron overload in the blood. The erythrocytes cannot be supplied with iron from the blood, resulting in anemia after birth, which manifests as pallor, fatigue and slow growth. The iron accumulates in the liver with hepatic symptoms manifested in adolescence or early adulthood. Mutations in the SLC11A2 gene cause this disorder, because a transporter protein for divalent metal ions is reduced in quantity and/or function or the transporter is mislocalized. This disorder is also inherited in an autosomal recessive manner. Other forms of inherited anemias (hemoglobinopathies, erythrocyte membrane defects, enzyme deficiencies, etc.) are investigated applying the panel in parallel via the additional genes comprised. The DNA diagnostic yield depends mainly on clinical pre-characterization, it should allow to assign more than 50% of cases. Therefore, however, a negative molecular genetic result can by no means exclude the clinical diagnosis.

Referenz: https://doi.org/10.1182/blood.2019004083

• Alias: Anemia, hypochromic microcytic, with defect in iron metabolism
• Alias: Eisenmangelanämie, eisenrefraktäre
• Alias: IRIDA syndrome
• Alias: IRIDA-Syndrom
• Alias: Iron-handling disorder, hereditary
• Allelic: Buruli ulcer, susceptibility to (SLC11A1)
• Allelic: Delta-beta thalassemia (HBB)
• Allelic: Dystonia 9 (SLC2A1)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Allelic: Erythrocytosis 6 (HBB)
• Allelic: Erythrocytosis 7 (HBA1, HBA2)
• Allelic: Even-plus syndrome (HSPA9)
• Allelic: Hemoglobin H disease, deletional + nondeletional (HBA2)
• Allelic: Hemoglobin H disease, nondeletional (HBA1)
• Allelic: Hereditary persistence of fetal hemoglobin (HBB)
• Allelic: Malaria, resistance to (HBB)
• Allelic: Methemoglobinemia, alpha type (HBA1)
• Allelic: Methemoglobinemia, beta type (HBB)
• Allelic: Mycobacterium tuberculosis, susceptibility to infection by (SLC11A1)
• Allelic: Pulmonary disease, chronic obstructive, susceptibility to (HMOX1)
• Allelic: Spasticity, childhood-onset, with hyperglycinemia (GLRX5)
• Allelic: Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Allelic: Thalassemia, alpha- (HBA2)
• Allelic: Thalassemia, beta (HBB)
• Allelic: Thalassemia-beta, dominant inclusion-body (HBB)
• Allelic: Thalassemias, alpha- (HBA1)
• Anemia, hypochromic microcytic, with iron overload 1 (SLC11A2)
• Anemia, hypochromic microcytic, with iron overload 2 (STEAP3)
• Anemia, neonatal hemolytic, fatal or near-fatal (SPTB)
• Anemia, sideroblastic, 1 (ALAS2)
• Anemia, sideroblastic, 2, pyridoxine-refractory (SLC25A38)
• Anemia, sideroblastic, 3, pyridoxine-refractory (GLRX5)
• Anemia, sideroblastic, 4 (HSPA9)
• Atransferrinemia (TF)
• Elliptocytosis-1 (EPB41)
• Elliptocytosis-2 (SPTA1)
• Elliptocytosis-3 (SPTB)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Heinz body anemia (HBA2, HBB)
• Heinz body anemias, alpha- (HBA1)
• Heme oxygenase-1 deficiency (HMOX1)
• Iron-refractory iron deficiency anemia (TMPRSS6)
• Myelodysplastic syndrome, somatic (SF3B1)
• Protoporphyria, erythropoietic, XL (ALAS2)
• Pyridoxine-refractory sideroblastic anemia [panelapp] (SLC2A1)
• Pyropoikilocytosis (SPTA1)
• Sickle cell anemia (HBB)
• Spherocytosis, type 2 (SPTB)
• Spherocytosis, type 3 (SPTA1)