TY - JOUR T1 - Efficacy of intravenous immunoglobulin therapy in giant cell hepatitis with autoimmune hemolytic anemia: A multicenter study. JF - Clin Res Hepatol Gastroenterol Y1 - 2015 A1 - Marsalli, Giulia A1 - Nastasio, Silvia A1 - Sciveres, Marco A1 - Calvo, Pier Luigi A1 - Ramenghi, Ugo A1 - Gatti, Simona A1 - Albano, Veronica A1 - Lega, Sara A1 - Ventura, Alessandro A1 - Maggiore, Giuseppe AB -

BACKGROUND AND OBJECTIVE: Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare disease of infancy, of possible autoimmune mechanism with poor prognosis due to its scarce response to immunosuppressive drugs. The aim of this retrospective multicenter study was to evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) treatment in inducing and maintaining remission of the liver disease, in patients with GCH-AHA.

METHODS: Seven children with GCH-AHA, four newly diagnosed, and three in relapse, being treated with different therapies, received one to three IVIg infusions (0.5 to 2g/kg) in association with other immunosuppressive drugs. Subsequently five of them received monthly sequential IVIg infusions (mean 13.4, range 7-24).

RESULTS: IVIg infusions as first-line therapy associated with prednisone and other immunosuppressive drugs significantly (P=0.04) reduced the aminotransferase activity in all patients and normalized prothombin activity in the only patient with severe liver dysfunction. Sequential monthly IVIg infusions determined a steroid-sparing effect and allowed a complete or partial remission in all patients, although with temporary efficacy, since relapse of the hemolytic anemia and/or of liver disease occurred in all patients. IVIg infusions were associated with mild side effects in two patients.

CONCLUSIONS: IVIg infusion can be safely and effectively administered in patients with severe GCH-AHA at diagnosis, or in case of relapse, in association with other immunosuppressive drugs. Repeated IVIg infusions may help maintain remission, however, due to their temporary efficacy, they should not be routinely employed.

U1 - http://www.ncbi.nlm.nih.gov/pubmed/26138133?dopt=Abstract ER - TY - JOUR T1 - Clinical features and follow-up in patients with 22q11.2 deletion syndrome. JF - J Pediatr Y1 - 2014 A1 - Cancrini, Caterina A1 - Puliafito, Pamela A1 - Digilio, Maria Cristina A1 - Soresina, Annarosa A1 - Martino, Silvana A1 - Rondelli, Roberto A1 - Consolini, Rita A1 - Ruga, Ezia Maria A1 - Cardinale, Fabio A1 - Finocchi, Andrea A1 - Romiti, Maria Luisa A1 - Martire, Baldassarre A1 - Bacchetta, Rosa A1 - Albano, Veronica A1 - Carotti, Adriano A1 - Specchia, Fernando A1 - Montin, Davide A1 - Cirillo, Emilia A1 - Cocchi, Guido A1 - Trizzino, Antonino A1 - Bossi, Grazia A1 - Milanesi, Ornella A1 - Azzari, Chiara A1 - Corsello, Giovanni A1 - Pignata, Claudio A1 - Aiuti, Alessandro A1 - Pietrogrande, Maria Cristina A1 - Marino, Bruno A1 - Ugazio, Alberto Giovanni A1 - Plebani, Alessandro A1 - Rossi, Paolo KW - Abnormalities, Multiple KW - Adolescent KW - Adult KW - Age Factors KW - Child KW - Child, Preschool KW - Chromosomes, Human, Pair 22 KW - Delayed Diagnosis KW - Developmental Disabilities KW - DiGeorge Syndrome KW - Disease Progression KW - Early Diagnosis KW - Female KW - Follow-Up Studies KW - Genetic Testing KW - Humans KW - Infant KW - Infant, Newborn KW - Male KW - Monitoring, Physiologic KW - Prospective Studies KW - Retrospective Studies KW - Risk Assessment KW - Severity of Illness Index KW - Sex Factors KW - Time Factors KW - Young Adult AB -

OBJECTIVE: To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease.

STUDY DESIGN: A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis.

RESULTS: The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P = .015) and speech disorders (P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis.

CONCLUSIONS: Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.

VL - 164 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24657119?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 -