Co-inheritance of Hb Hershey [beta70(E14) Ala-->Gly] and Hb La Pommeraie [beta133(H11)Val-->Met] in a Sicilian subject.

OBJECTIVES: This report represents the first observation in Sicily of two rare beta-globin gene variants, Hb Hershey [beta70(E14) Ala-->Gly] and Hb La Pommeraie [beta133(H11)Val-->Met], found in a 35-year-old male patient from Messina, in the north-east of Sicily during population screening for hemoglobinopathies. METHODS: The occurrence of the Hb variants was assessed by cation exchange chromatography while complete blood counts were obtained using automatic cell counters. Red cell lysates were analyzed by electrophoresis at alkaline and acid pH. Stability of hemoglobin was checked by the isopropanol precipitation test and by the heat tests while inclusion bodies and reticulocyte count were determined by incubation of blood samples with brilliant cresyl blue. Molecular analysis was performed by DNA sequencing of beta- and alpha-globin genes. RESULTS: We observed an abnormally high performance liquid chromatography elution with a slight reduction in mean corpuscular volume and mean corpuscular haemoglobin parameters and mutations at codon 70 GCC-->GGC (Hb Hershey) and at codon 133 GTG-->ATG (Hb La Pommeraie) in beta-globin gene. CONCLUSION: Family analysis of three generations demonstrated the presence of these two mutations in trans. So it was possible to describe the phenotypes of these variants in a heterozygous state and in double heterozygous state.

Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation.

In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life.

Role of polymorphic sequences 5' to the G(gamma) gene and 5' to the beta gene on the homozygous beta thalassemic phenotype.

Sixty-seven homozygous male and female thalassemic patients with different phenotypes, aged between 8 and 33 years, were divided into three groups, according to the severity of their beta-thalassemia (thal) mutations. We investigated whether some co-inherited genetic factors could influence the phenotype. Patients with milder beta-thal defects, homozygotes or compound heterozygotes for the IVS-I-6 (T-->C) or -87 (C-->G) mutations had a milder disease. In addition, determination of the co-inheritance of the -158 (C-->T) G(gamma) polymorphism and the (AT)9T5 repeat motif in the region -540 to -525, 5' to the beta-globin gene, showed that in some patients with severe or mild/severe beta-thal mutations, linked to haplotype III, there was higher Hb F expression. We conclude that in homozygous beta-thal patients, the severity of the mutations is the most important factor influencing the phenotype, but some polymorphisms such as the -158 (C-->T) G(gamma) and (AT)9T5 repeat motif, increasing the Hb F expression and ameliorate the clinical course of the disease.