The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022.
J Clin Endocrinol Metab
; 109(9): 2349-2357, 2024 Aug 13.
Article
em En
| MEDLINE
| ID: mdl-38408297
ABSTRACT
CONTEXT In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM). 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 1103 340 (NDM) and 11 240 082 (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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus
Limite:
Female
/
Humans
/
Infant
/
Male
/
Newborn
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article