The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Rapini Novella, Delvecchio Maurizio, Mucciolo Mafalda, Ruta Rosario, Rabbone Ivana, Cherubini Valentino, Zucchini Stefano, Cianfarani Stefano, Prandi Elena, Schiaffini Riccardo, Bizzarri Carla, Piccini Barbara, Maltoni Giulio, Predieri Barbara, Minuto Nicola, Di Paola Rossella, Giordano Mara, Tinto Nadia, Grasso Valeria, Russo Lucia, Tiberi Valentina, Scaramuzza Andrea, Frontino Giulio, Maggio Maria Cristina, Musolino Gianluca, Piccinno Elvira, Tinti Davide, Carrera Paola, Mozzillo Enza, Cappa Marco, Iafusco Dario, Bonfanti Riccardo, Novelli Antonio, Barbetti Fabrizio, Diabetes Study Group of Italian Society for Pediatric Endocrinology and Diabetes (ISPED)
Аннотация
OBJECTIVE: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS).
METHODS: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset.
RESULTS: Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin.
CONCLUSION: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy.