Hearing loss in beta-thalassaemia: An Italian multicentre case-control study.

BACKGROUND: Despite numerous studies, the true scenario of hearing loss in beta-thalassaemia remains rather nebulous. MATERIALS AND METHODS: Pure tone audiometry, chelation therapy, demographics and laboratory data of 376 patients (mean age 38.5 ± 16.6 years, 204 females, 66 non-transfusion-dependent) and 139 healthy controls (mean age 37.6 ± 17.7 years, 81 females) were collected. RESULTS: Patient and control groups did not differ for age (p = 0.59) or sex (p = 0.44). Hypoacusis rate was higher in patients (26.6% vs. 7.2%; p < 0.00001), correlated with male sex (32.6% in males vs. 21.8% in females; p = 0.01) and it was sensorineural in 79/100. Hypoacusis rate correlated with increasing age (p = 0.0006) but not with phenotype (13/66 non-transfusion-dependent vs. 87/310 transfusion-dependent patients; p = 0.16). Sensorineural-notch prevalence rate did not differ between patients (11.4%) and controls (12.2%); it correlated with age (p = 0.01) but not with patients' sex or phenotype. Among adult patients without chelation therapy, the sensorineural hypoacusis rate was non-significantly lower compared to chelation-treated patients while it was significantly higher compared to controls (p = 0.003). CONCLUSIONS: Sensorineural hypoacusis rate is high in beta-thalassaemia (about 21%) and it increases with age and in males while disease severity or chelation treatment seems to be less relevant. The meaning of sensorineural-notch in beta-thalassaemia appears questionable.

Role of the cold shock domain protein A in the transcriptional regulation of HBG expression.

Impaired switching from fetal haemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal haemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate ß-thalassaemia and sickle cell anaemia. Fetal haemoglobin levels are regulated by complex mechanisms involving factors linked or not to the ß-globin gene (HBB) locus. To search for factors putatively involved in the expression of the γ-globin genes (HBG1, HBG2), we examined the reticulocyte transcriptome of three siblings who had different HbF levels and different degrees of ß-thalassaemia severity although they had the same ΗBA- and ΗΒB cluster genotypes. By mRNA differential display we isolated the cDNA coding for the cold shock domain protein A (CSDA), also known as dbpA, previously reported to interact in vitro with the HBG2 promoter. Expression studies performed in K562 and in primary erythroid cells showed an inverse relationship between HBG and CSDA expression levels. Functional studies performed by Chromatin Immunoprecipitation and reporter gene assays in K562 cells demonstrated that CSDA is able to bind the HBG2 promoter and suppress its expression. Therefore, our study demonstrated that CSDA is a trans-acting repressor factor of HBG expression and modulates the HPFH phenotype.

Treatment with short-term, high-dose cyclosporin A in children with refractory chronic idiopathic thrombocytopenic purpura.

We report on 14 children (seven boys, seven girls) with chronic idiopathic thrombocytopenic purpura (ITP) refractory to multiple treatments, who were given a short-term therapy (range between 6 and 10 weeks) with high doses of cyclosporin A (CyA) (median, 10 mg/kg/d). Six patients experienced adverse events and one developed severe systemic mycosis during therapy. A complete response (CR) was observed in four patients and a partial response (PR) in three patients. Only the four CR patients, who were all girls, had a sustained response. These data suggest that CyA may be effective in some children with chronic symptomatic ITP.