Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy
Author:
Bonfanti Riccardo1, Iafusco Dario2, Rabbone Ivana3, Diedenhofen Giacomo4, Bizzarri Carla5, Patera Patrizia Ippolita5, Reinstadler Petra6, Costantino Francesco7, Calcaterra Valeria8, Iughetti Lorenzo9, Savastio Silvia10, Favia Anna11, Cardella Francesca12, Lo Presti Donatella13, Girtler Ylenia6, Rabbiosi Sarah6, D’Annunzio Giuseppe14, Zanfardino Angela2, Piscopo Alessia2, Casaburo Francesca2, Pintomalli Letizia15, Russo Lucia5, Grasso Valeria5, Minuto Nicola14, Mucciolo Mafalda16, Novelli Antonio16, Marucci Antonella17, Piccini Barbara18, Toni Sonia18, Silvestri Francesca7, Carrera Paola1920, Rigamonti Andrea1, Frontino Giulio1, Trada Michela3, Tinti Davide3, Delvecchio Maurizio21, Rapini Novella4, Schiaffini Riccardo4, Mammì Corrado15, Barbetti Fabrizio45, _ _, _ _, Aloe Monica, Amadeo Simona, Arnaldi Claudia, Bassi Marta, Beccaria Luciano, Benelli Marzia, Maria Berioloi Giulia, Bertelli Enrica, Biagioni Martina, Bobbio Adriana, Boccato Stefano, Bologna Oriana, Bontempi Franco, Bonura Clara, Bracciolini Giulia, Brufani Claudia, Bruzzi Patrizia, Buono Pietro, Calcaterra Valeria, Cardani Roberta, Cardinale Giuliana, Casertano Alberto, Cristina Castiglione Maria, Cauvin Vittoria, Cherubini Valentino, Chiarelli Franco, Chiari Giovanni, Cianfarani Stefano, Cirillo Dante, Citriniti Felice, Coccioli Susanna, Cogliardi Anna, Confetto Santino, Contreas Giovanna, Corò Anna, Corsini Elisa, Cresta Nicoletta, De Berardinis Fiorella, De Donno Valeria, De Filippo Giampaolo, De Marco Rosaria, Deodati Annalisa, Faleschini Elena, Fattorusso Valentina, Favalli Valeria, Felappi Barbara, Ferrito Lucia, Fichera Graziella, Fontana Franco, Fornari Elena, Franceschi Roberto, Franco Francesca, Franzese Adriana, Paola Frongia Anna, Gaiero Alberto, Gallo Francesco, Gargantini Luigi, Giani Elisa, Giorgetti Chiara, Bianchi Giulia, Graziani Vanna, Gualtieri Antonella, Guasti Monica, Iannicelli Gennaro, Iannilli Antonio, Giovanna Ignaccolo, Ingletto Dario, Innaurato Stefania, Inzaghi Elena, Iovane Brunella, Kaufmann Peter, La Loggia Alfonso, Lapolla Rosa, Lasagni Anna, Lazzaro Nicola, Lenzi Lorenzo, Lera Riccardo, Levantini Gabriella, Lombardo Fortunato, Lonero Antonella, Longhi Silvia, Lucchesi Sonia, Paola Guerraggio Lucia, Lucieri Sergio, Macellaro Patrizia, Maffeis Claudio, Mainetti Bendetta, Maltoni Giulio, Mameli Chiara, Mammì Francesco, Luisa Manca-Bitti Maria, Manco Melania, Marino Monica, Mariano Matteo, Marigliano Marco, Marsciani Alberto, Mastrangelo Costanzo, Cristina Matteoli Maria, Mazzali Elena, Meschi Franco, MIgliaccio Antonella, Morandi Anita, Morganti Gianfranco, Mozzillo Enza, Musolino Gianluca, Nugnes Rosa, Ortolani Federica, Pardi Daniela, Pascarella Filomena, Passanisi Stefano, Pedini Annalisa, Pennati Cristina, Perrotta Angelo, Peruzzi Sonia, Peverelli Paola, Pezzino Giulia, Claudia Piona Anita, Piredda Gavina, Pistone Carmelo, Prandi Elena, Pedieri Barbara, Di Bonito Procolo, Pulcina Anna, Quinci Maria, Randazzo Emioli, Ricciardi Rossella, Ripoli Carlo, Roppolo Rosanna, Rutigliano Irene, Sabbio Alberto, salardi Silvana, Salvatoni Alessandro, Saporiti Anna, Sardi Rita, Scanu Mariapiera, Scaramuzza Andrea, Eleonardo Schiven ,, Secco Andrea, Sessa Linda, Sogno Valin Paola, Sordelli Silvia, Spallino Luisa, Stagi Stefano, Stamati Filomena, Suprani Tosca, Talarico Valentina, Timapanaro Tiziana, Tirendi Antonella, Tomaselli Letizia, Tornese Gianluca, Andrea Trettene Adolfo, Tumini Stefano, Valerio Giuliana, Ventrici Claudia, Viscardi Matteo, Zaffani Silvana, Zampolli Maria, Zanette Giorgio, Zecchino Clara, Antonietta Zedda Maria, Zonca Silvia, Zucchini Stefano
Affiliation:
1. 1Department of Pediatrics, Pediatric Diabetology Unit, Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy 2. 2Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy 3. 3Department of Pediatrics, University of Turin, Turin, Italy 4. 4Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy 5. 5Diabetology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy 6. 6S. Maurizio Hospital, Bolzano, Italy 7. 7Department of Pediatrics, University of Rome Sapienza, Rome, Italy 8. 8Department of Internal Medicine and Therapeutics, Pediatric and Adolescent Unit, University of Pavia and Department of Pediatrics, ‘Vittore Buzzi’ Children’s Hospital, Milan, Italy 9. 9Department of Medical and Surgical Sciences of Mother, Children and Adults, Pediatric Unit, University of Modena and Reggio Emilia, Modena, Italy 10. 10SCDU of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale, Novara, Piemonte, Italy 11. 11Department of Pediatrics, S. Maria degli Angeli Hospital, Pordenone, Italy 12. 12Regional Center for Pediatric Diabetes, Giovanni Di Cristina Children Hospital, Palermo, Italy 13. 13Regional Center for Pediatric Diabetes, AOU, Policlinico Vittorio Emanuele, Catania, Italy 14. 14Regional Center for Pediatric Diabetes, IRCCS Istituto Giannina Gaslini, Genoa, Italy 15. 15Great Metropolitan Hospital BMM, Reggio Calabria, Italy 16. 16Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy 17. 17Research Unit of Diabetes and Endocrine Diseases, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy 18. 18Regional Center for Pediatric Diabetes, Meyer University Children’s Hospital, Florence, Italy 19. 19San Raffaele Scientific Institute, Center for Omics sciences @OSR, Genomics for the Diagnosis of Human Pathologies, Milan, Italy 20. 20San Raffaele Scientific Institute, Laboratory of Molecular Genetics and Cytogenetics, Milan, Italy 21. 21Department of Metabolic Diseases, Clinical Genetics and Diabetology, Giovanni XXIII Children’s Hospital, Bari, Italy
Abstract
Objective
Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features.
Design
Retrospective analysis of the Italian data set of patients with TNDM.
Methods
Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared.
Results
Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy.
Conclusions
If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
Subject
Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism
Cited by
16 articles.
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