TY - JOUR T1 - Organizing national responses for rare blood disorders: the Italian experience with sickle cell disease in childhood. JF - Orphanet J Rare Dis Y1 - 2013 A1 - Colombatti, Raffaella A1 - Perrotta, Silverio A1 - Samperi, Piera A1 - Casale, Maddalena A1 - Masera, Nicoletta A1 - Palazzi, Giovanni A1 - Sainati, Laura A1 - Russo, Giovanna KW - Adolescent KW - Anemia, Sickle Cell KW - Child KW - Child, Preschool KW - Disease Management KW - Female KW - Hematologic Diseases KW - Humans KW - Infant KW - Infant, Newborn KW - Italy KW - Male KW - Neonatal Screening KW - Rare Diseases AB -

BACKGROUND: Sickle cell disease (SCD) is the most frequent hemoglobinopathy worldwide but remains a rare blood disorder in most western countries. Recommendations for standard of care have been produced in the United States, the United Kingdom and France, where this disease is relatively frequent because of earlier immigration from Africa. These recommendations have changed the clinical course of SCD but can be difficult to apply in other contexts. The Italian Association of Pediatric Hematology Oncology (AIEOP) decided to develop a common national response to the rising number of SCD patients in Italy with the following objectives: 1) to create a national working group focused on pediatric SCD, and 2) to develop tailored guidelines for the management of SCD that could be accessed and practiced by those involved in the care of children with SCD in Italy.

METHODS: Guidelines, adapted to the Italian social context and health system, were developed by 22 pediatric hematologists representing 54 AIEOP centers across Italy. The group met five times for a total of 128 hours in 22 months; documents and opinions were circulated via web.

RESULTS: Recommendations regarding the prevention and treatment of the most relevant complications of SCD in childhood adapted to the Italian context and health system were produced.

CONCLUSIONS: Creating a network of physicians involved in the day-to-day care of children with SCD is feasible in a country where it remains rare. Providing hematologists, primary and secondary care physicians, and caregivers across the country with web-based guidelines for the management of SCD tailored to the Italian context is the first step in building a sustainable response to a rare but emerging childhood blood disorder and in implementing the World Health Organization's suggestion "to design (and) implement … comprehensive national integrated programs for the prevention and management of SCD".

VL - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24139596?dopt=Abstract ER - TY - JOUR T1 - Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIbα (Bolzano mutation). JF - Haematologica Y1 - 2012 A1 - Noris, Patrizia A1 - Perrotta, Silverio A1 - Bottega, Roberta A1 - Pecci, Alessandro A1 - Melazzini, Federica A1 - Civaschi, Elisa A1 - Russo, Sabina A1 - Magrin, Silvana A1 - Loffredo, Giuseppe A1 - Di Salvo, Veronica A1 - Russo, Giovanna A1 - Casale, Maddalena A1 - De Rocco, Daniela A1 - Grignani, Claudio A1 - Cattaneo, Marco A1 - Baronci, Carlo A1 - Dragani, Alfredo A1 - Albano, Veronica A1 - Jankovic, Momcilo A1 - Scianguetta, Saverio A1 - Savoia, Anna A1 - Balduini, Carlo L KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Bernard-Soulier Syndrome KW - Child KW - Child, Preschool KW - Family Health KW - Female KW - Heterozygote KW - Humans KW - Infant KW - Italy KW - Male KW - Membrane Glycoproteins KW - Middle Aged KW - Mutation, Missense KW - Platelet Aggregation KW - Platelet Count KW - Platelet Glycoprotein GPIb-IX Complex KW - Polymorphism, Genetic KW - Thrombocytopenia KW - Thrombopoietin KW - Tubulin KW - Young Adult AB -

BACKGROUND: Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIbα, GPIbβ, or GPIX and is typically inherited as a recessive disease. However, some years ago it was shown that the monoallelic c.515C>T transition in the GPIBA gene (Bolzano mutation) was responsible for macrothrombocytopenia in a few Italian patients.

DESIGN AND METHODS: Over the past 10 years, we have searched for the Bolzano mutation in all subjects referred to our institutions because of an autosomal, dominant form of thrombocytopenia of unknown origin.

RESULTS: We identified 42 new Italian families (103 cases) with a thrombocytopenia induced by monoallelic Bolzano mutation. Analyses of the geographic origin of affected pedigrees and haplotypes indicated that this mutation originated in southern Italy. Although the clinical expression was variable, patients with this mutation typically had a mild form of Bernard-Soulier syndrome with mild thrombocytopenia and bleeding tendency. The most indicative laboratory findings were enlarged platelets and reduced GPIb/IX/V platelet expression; in vitro platelet aggregation was normal in nearly all of the cases.

CONCLUSIONS: Our study indicates that monoallelic Bolzano mutation is the most frequent cause of inherited thrombocytopenia in Italy, affecting 20% of patients recruited at our institutions during the last 10 years. Because many people from southern Italy have emigrated during the last century, this mutation may have spread to other countries.

VL - 97 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21933849?dopt=Abstract ER - TY - JOUR T1 - Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families. JF - Blood Y1 - 2011 A1 - Noris, Patrizia A1 - Perrotta, Silverio A1 - Seri, Marco A1 - Pecci, Alessandro A1 - Gnan, Chiara A1 - Loffredo, Giuseppe A1 - Pujol-Moix, Núria A1 - Zecca, Marco A1 - Scognamiglio, Francesca A1 - De Rocco, Daniela A1 - Punzo, Francesca A1 - Melazzini, Federica A1 - Scianguetta, Saverio A1 - Casale, Maddalena A1 - Marconi, Caterina A1 - Pippucci, Tommaso A1 - Amendola, Giovanni A1 - Notarangelo, Lucia D A1 - Klersy, Catherine A1 - Civaschi, Elisa A1 - Balduini, Carlo L A1 - Savoia, Anna KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Ankyrin Repeat KW - Child KW - Cohort Studies KW - Family KW - Female KW - Gene Frequency KW - Humans KW - Inheritance Patterns KW - Male KW - Middle Aged KW - Mutation KW - Pedigree KW - Thrombocytopenia KW - Transcription Factors KW - Young Adult AB -

Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal dominant thrombocytopenia and only 2 families were known. However, we recently identified mutations in the 5'-untranslated region of the ANKRD26 gene in 9 THC2 families. Here we report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. Because THC2 affected 21 of the 210 families in our database, it has to be considered one of the less rare forms of inherited thrombocytopenia. Analysis of all 21 families with ANKRD26 mutations identified to date revealed that thrombocytopenia and bleeding tendency were usually mild. Nearly all patients had no platelet macrocytosis, and this characteristic distinguishes THC2 from most other forms of inherited thrombocytopenia. In the majority of cases, platelets were deficient in glycoprotein Ia and α-granules, whereas in vitro platelet aggregation was normal. Bone marrow examination and serum thrombopoietin levels suggested that thrombocytopenia was derived from dysmegakaryopoiesis. Unexplained high values of hemoglobin and leukocytes were observed in a few cases. An unexpected finding that warrants further investigation was a high incidence of acute leukemia. Given the scarcity of distinctive characteristics, the ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias.

VL - 117 IS - 24 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21467542?dopt=Abstract ER -