Intravenous Iron Sucrose for Children With Iron Deficiency Anemia.

Iron deficiency anemia (IDA) is the most common nutritional deficiency in children. Most children with IDA are treated with oral iron preparations. However, intravenous (IV) iron is an alternative for children with severe IDA who have difficulty in adhering to or absorbing oral iron. We sought to describe the safety and effectiveness of IV iron sucrose for treatment of IDA in children. Pharmacy records of children who received IV iron sucrose at a children's hospital between 2004 and 2014 were reviewed. Laboratory markers of anemia and iron studies were obtained and preinfusion and postinfusion values were compared. Records were also reviewed for adverse reactions. A total of 142 patients received IV iron sucrose over 10 years. The mean age was 11 years, 9 months. One patient of 142 developed cough and wheezing during the infusion. No other adverse events were found. IV iron sucrose resulted in a statistically significant and clinically meaningful increase in hemoglobin, mean corpuscular volume, serum iron, ferritin, and % iron saturation, with a corresponding decrease in total iron binding capacity. The use of IV iron sucrose in pediatric patients with IDA is safe and leads to a moderate increase in hemoglobin and substantial improvement in iron studies.

A T-to-G transversion at nucleotide -567 upstream of HBG2 in a GATA-1 binding motif is associated with elevated hemoglobin F.

Increased fetal hemoglobin (Hb F; alpha(2)gamma(2)) production in adults can ameliorate the clinical severity of sickle cell disease and beta-thalassemia major. Thus, understanding the regulation of gamma-globin gene expression and its silencing in adults has potential therapeutic implications. We studied a father and son in an Iranian-American family who had elevated Hb F levels and found a novel T-to-G transversion at nucleotide (nt) -567 of the HBG2 promoter. This mutation alters a GATA-1 binding motif to a GAGA sequence located within a previously identified silencing element. DNA-protein binding assays showed that the GATA motif of interest is capable of binding GATA-1 transcription factor in vitro and in vivo. Truncation analyses of the HBG2 promoter linked to a luciferase reporter gene revealed a negative regulatory activity present between nt -675 and -526. In addition, the T-to-G mutation at the GATA motif increased the promoter activity by two- to threefold in transiently transfected erythroid cell lines. The binding motif is uniquely conserved in simian primates with a fetal pattern of gamma-globin gene expression. These results suggest that the GATA motif under study has a functional role in silencing gamma-globin gene expression in adults. The T-to-G mutation in this motif disrupts GATA-1 binding and the associated repressor complex, abolishing its silencing effect and resulting in the up-regulation of gamma-globin gene expression in adults.

Antiphospholipid antibodies and Down syndrome: a case series.

To describe the clinical profiles of five patients with Down syndrome and elevated levels of antiphospholipid antibodies. Medical records of all 149 patients screened for anticardiolipin antibodies (aCL) in the pediatric hematology or pediatric rheumatology clinics at New England Medical Center between 1996 and 1998 were retrospectively reviewed, and patients with Down syndrome identified. Thirty-four patients (23%) had elevated IgG titers of aCL antibodies. Of these, five had Down syndrome (15%). Two presented with discoloration of the distal digits, and one each with thrombocytopenia, autoimmune hepatitis, and undifferentiated autoimmune disease. The mothers of two of the four individuals with available family history had experienced frequent miscarriages. An association may exist between Down syndrome and antiphospholipid antibodies, in particular an increased frequency of aCL antibodies. Screening patients with Down syndrome and certain clinical findings may prove useful.