Safety and Efficacy of the New Combination Iron Chelation Regimens in Patients with Transfusion-Dependent Thalassemia and Severe Iron Overload.

The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone in a large group of transfusion-dependent thalassemia patients with high values of serum ferritin and/or magnetic resonance, indicative of severe liver and cardiac iron accumulation. Sixteen adults with transfusion-dependent thalassemia were treated simultaneously with deferasirox plus desferrioxamine, while another 42 patients (seven children) were treated with deferasirox plus deferiprone. The hepatic and cardiac iron overload was assessed prior to treatment and then annually with magnetic resonance imaging, and the serum ferritin was measured monthly.

Impact of the direct-acting antiviral agents (DAAs) on chronic hepatitis C in Sardinian patients with transfusion-dependent Thalassemia major.

Background And Aims: Direct antiviral agents (DAAs) have revolutionised the standard of care for the treatment of hepatitis even in patients with hemoglobinopathies. The aim of this study is to show how, thanks to DAAs, HCV infection has been substantially eradicated in one of the biggest Centres for the management of Thalassemia in Europe.

Methods: Thalassemia major patients regularly transfused and iron chelated in Cagliari (Italy) who were HCV-RNA positive were evaluated for the potential prescription of antiviral therapy.

Quality of life in Sardinian patients with transfusion-dependent Thalassemia: a cross-sectional study.

Purpose: The aim of this study has been to evaluate the physical, psychological, and social well-being in a large group of Sardinian adult patients with transfusion-dependent beta-Thalassemia when compared with a group of healthy subjects of the same age and geographical extraction.

Methods: Male or female patients ≥ 18 years of age with Thalassemia major on regular transfusion at Thalassemia Center in Cagliari (Italy) were requested to complete the World Health Organization Quality of life-BREF (WHOQOL-BREF) questionnaire. The WHOQOL-BREF was also made available online to age- and sex-matched non-thalassemic adult subjects living in Sardinia.

Thalassemia major between liver and heart: Where we are now.

The aim of the study was to assess the current state in terms of liver and heart iron overload as well as of liver and heart related morbidity and mortality in a large cohort of thalassemia patients. Myocardial iron loading was present in 28.9% patients, which was severe in 3.

Wilson's disease.

Wilson's disease (WD) is a disorder of copper transport resulting from the defective function of a copper transporting P-type ATPase, ATP7B. The WD incidence is approximately 1/50-10,000 live births worldwide. Clinical manifestations of WD may be of any kind, but usually the symptoms of presentation are hepatic or neuropsychiatric, with a vast range of disturbances for both groups of symptoms.

The homozygosity index (HI) approach reveals high allele frequency for Wilson disease in the Sardinian population.

Wilson disease (WD) is an autosomal recessive disorder resulting in pathological progressive copper accumulation in liver and other tissues. The worldwide prevalence (P) is about 30/million, while in Sardinia it is in the order of 1/10,000. However, all of these estimates are likely to suffer from an underdiagnosis bias.

Wilson's disease in two consecutive generations: the detection of three mutated alleles in the ATP7B gene in two Sardinian families.

Background: Wilson's disease diagnosis is still a challenge for clinicians.

Aim: To underline the importance of genetic testing in carrier detection and diagnosis of atypical Wilson's disease cases.

Methods: Two families with Wilson's disease in two consecutive generations were analysed with clinical, biochemical and genetic testing.

Mutation analysis of the ATP7B gene in a new group of Wilson's disease patients: contribution to diagnosis.

Wilson's disease (WD), an autosomal recessive disorder of copper transport with a broad range of genotypic and phenotypic characteristics, results from mutations in the ATP7B gene. Herein we report the results of mutation analysis of the ATP7B gene in a group of 118 Wilson disease families (236 chromosomes) prevalently of Italian origin. Using DNA sequencing we identified 83 disease-causing mutations.

Feasibility of RNA studies on illegitimate transcription for molecular characterization of splicing mutations in the ATP7B gene: a case report.

Approximately 520 Wilson disease-causing mutations in the ATP7B gene have been described to date. In this study we report DNA and RNA analyses carried out for molecular characterization of a consensus sequence splicing mutation found in homozygosity in a Swiss Wilson disease patient. RNA analysis of 1946 +6 T→C in both the peripheral lymphoblasts and liver resulted in the production in the propositus of only an alternative transcript lacking exons 6, 7, and 8 resulting most likely in alterations of cell biochemistry and disease.

DNA and RNA studies for molecular characterization of a gross deletion detected in homozygosity in the NH2-terminal region of the ATP7B gene in a Wilson disease patient.

Wilson disease is an autosomal recessive disorder caused by defective function of the copper transporting protein ATP7B. Approximately 520 Wilson disease-causing mutations have been described to date. In this study we report the use of DNA and RNA analysis for molecular characterization of a gross deletion of the ATP7B gene detected in homozygosity in a Wilson disease patient.

Molecular analysis of glycogen storage disease type Ib in Sardinian population: evidence for a founder effect.

We describe epidemiological, genetic, and clinical data of the 1124-2del mutation in the G6PT gene, detected in homozygosity in three glycogen storage disease type Ib patients of Sardinian origin. This mutation was found to be associated with four sequence variations: c.593 A>T (p.

Development of TaqMan allelic specific discrimination assay for detection of the most common Sardinian Wilson's disease mutations. Implications for genetic screening.

Wilson's disease (WD) is an autosomal recessive disorder caused by a defective function of the copper transporting ATP7B protein. Analysis of ATP7B gene in the Sardinian population revealed the presence of six common mutations that together account for 85% of WD chromosomes. We have developed an automated approach for the detection of these 6 common Sardinian mutations based on TaqMan technology.

RNA analysis of consensus sequence splicing mutations: implications for the diagnosis of Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder caused by a defective function of the copper-transporting ATP7B protein. This results in progressive copper overload and consequent liver, brain, and kidney damage. Approximately 300 WD-causing mutations have been described to date.

High incidence and allelic homogeneity of Wilson disease in 2 isolated populations: a prerequisite for efficient disease prevention programs.

Objectives: Herein we report the results of mutation-based screening for Wilson disease (WD) in 2 isolated populations of Sardinia and the Greek island of Kalymnos.

Patients And Methods: Mutation analysis was performed in 110 and 9 WD families originating respectively from Sardinia and Kalymons using single-strand conformation polymorphism and sequencing methods. In Sardinia, a limited screening was performed for -441/-427del in 5290 newborns, whereas in Kalymnos 397 newborns underwent mutation screening for H1069Q and R969Q using appropriate methods.

Twenty-four novel mutations in Wilson disease patients of predominantly Italian origin.

Herein we report the results of mutation analysis of the ATP7B gene in a group of 134 Wilson disease (WD) families (268 chromosomes) prevalently of Italian origin. Using the SSCP and sequencing methods we identified 71 disease-causing mutations. Twenty-four were novel, while 19 more mutations already described, were identified in new populations in this study.

Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with beta-thalassemia major.

Background And Objectives: Deferasirox (ICL670) is a novel once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. This study evaluated the safety and tolerability of deferasirox in pediatric patients with transfusion-dependent beta-thalassemia major. Efficacy and pharmacokinetic assessments were secondary objectives.