Responsiveness to oral iron and ascorbic acid in a patient with IRIDA.

Mutations in TMPRSS6 gene cause iron-refractory iron deficiency anemia, a rare autosomal recessive disorder characterized by hypochromic microcytic anemia not responsive to oral iron therapy and partially responsive to parenteral iron administration. Here we report a female infant homozygous for a loss of function mutation in TMPRSS6 gene, who responded to oral iron therapy when supplemented with ascorbic acid.

Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation.

Variations at the KLF1 gene have been associated with a series of human erythroid phenotypes including the In-(Lu) phenotype, hereditary persistence of fetal hemoglobin, congenital dyserythropoietic anemia, borderline HbA(2) and increased red blood cell protoporphyrin. Natural mutations have shown that KLF1 regulates gamma globin gene expression and its role in the switching from fetal to adult globin expression has been suggested by experimental studies. In this paper we report that subjects with S270X KLF1 mutations show a decrease of HbF levels with increasing age, supporting in vivo the role of KLF1 in hemoglobin switching in humans.

Association of α globin gene quadruplication and heterozygous β thalassemia in patients with thalassemia intermedia.

Ten patients with thalassemia intermedia with variable severity and apparent simple heterozygosis for beta0 39 C>T nonsense mutation were submitted to clinical, hematologic and molecular studies. The presence of an unknown molecular defect (silent beta-thalassemia) unlinked to the beta cluster interacting with the heterozygous beta thalassemia, was previously postulated in these families. Analysis of the alpha globin gene cluster with PCR-based methods (MLPA, GAP-PCR, digestion with restriction enzymes) detected complex rearrangements in the alpha cluster.

Liver iron concentrations and urinary hepcidin in beta-thalassemia.

Background And Objectives: Patients with beta-thalassemia, like those with genetic hemochromatosis, develop iron overload due to increased iron absorption, and their iron burden is further exacerbated by transfusion therapy. Hepcidin, a hepatic hormone, regulates systemic iron homeostasis by inhibiting the absorption of iron from the diet and the recycling of iron by macrophages. In turn, hepcidin release is increased by iron loading and inhibited by erythropoietic activity.