1/3. Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.X-linked sideroblastic anemia (XLSA) in four unrelated male probands was caused by missense mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). All were new mutations: T647C, C1283T, G1395A, and C1406T predicting amino acid substitutions Y199H, R411C, R448Q, and R452C. All probands were clinically pyridoxine-responsive. The mutation Y199H was shown to be the first de novo XLSA mutation and occurred in a gamete of the proband's maternal grandfather. There was a significantly higher frequency of coinheritance of the hereditary hemochromatosis (HH) HFE mutant allele C282Y in 18 unrelated XLSA hemizygotes than found in the normal population, indicating a role for coinheritance of HFE alleles in the expression of this disorder. One proband (Y199H) with severe and early iron loading coinherited HH as a C282Y homozygote. The clinical and hematologic histories of two XLSA probands suggest that iron overload suppresses pyridoxine responsiveness. Notably, reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicate the value of combined phlebotomy and pyridoxine supplementation in the management of XLSA probands in order to prevent a downward spiral of iron toxicity and refractory anemia.- - - - - - - - - - ranking = 1keywords = phlebotomy (Clic here for more details about this article) |
2/3. Sideroblastic anaemia associated with iron overload treated by repeated phlebotomy.iron overload with prominent skin pigmentation and hepatic parenchymal siderosis is reported in a patient with refractory sideroblastic anaemia. Failure to reverse the sideroblastic changes or the anaemia with conventional therapy prompted us to use a graded phlebotomy programme. The rising haemoglobin level in spite of repeated venesections is support for this approach in selected patients with this diagnosis.- - - - - - - - - - ranking = 0.71428571428571keywords = phlebotomy (Clic here for more details about this article) |
3/3. Nonmyeloablative allogeneic hematopoietic stem cell transplantation for congenital sideroblastic anemia.Congenital sideroblastic anemia (CSA) is a dyserythropoietic disorder that leads to transfusion dependency and subsequent iron overload. Nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) was performed for a patient with CSA, who had contraindications to conventional allografting. Conditioning was fludarabine, low-dose total body irradiation and antithymocyte globulin, followed by peripheral blood stem cell transplant. cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. Complete donor chimerism was observed day 131. Early after transplant, the patient became transfusion independent, allowing a regular phlebotomy program. On day 190, refractory lactic acidosis followed by fatal cardiovascular collapse developed, without evidence of infection. Data from this case demonstrates that NST may correct the erythropoietic defect of CSA.- - - - - - - - - - ranking = 0.14285714285714keywords = phlebotomy (Clic here for more details about this article) |