Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy.

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.

• Authors: Riccardo Bonfanti, Dario Iafusco, Ivana Rabbone, Giacomo Diedenhofen, Carla Bizzarri, Patrizia Ippolita Patera, Petra Reinstadler, Francesco Costantino, Valeria Calcaterra, Lorenzo Iughetti, Silvia Savastio, Anna Favia, Francesca Cardella, Donatella Lo Presti, Ylenia Girtler, Sarah Rabbiosi, Giuseppe D'Annunzio, Angela Zanfardino, Alessia Piscopo, Francesca Casaburo, Letizia Pintomalli, Lucia Russo, Valeria Grasso, Nicola Minuto, Mafalda Mucciolo, Antonio Novelli, Antonella Marucci, Barbara Piccini, Sonia Toni, Francesca Silvestri, Paola Carrera, Andrea Rigamonti, Giulio Frontino, Michela Trada, Davide Tinti, Maurizio Delvecchio, Novella Rapini, Riccardo Schiaffini, Corrado Mammì, Fabrizio Barbetti, Diabetes Study Group of ISPED
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 184 Issue 4 Pg. 575-585 (Apr 2021) ISSN: 1479-683X [Electronic] England
• PMID: 33606663 (Publication Type: Comparative Study, Journal Article)

Chemical References

• ABCC8 protein, human
• Kir6.2 channel
• Potassium Channels, Inwardly Rectifying
• Sulfonylurea Receptors

Topics

• Datasets as Topic
• Diabetes Mellitus (classification, congenital, diagnosis, genetics, therapy)
• Diagnosis, Differential
• Diagnostic Techniques, Endocrine (standards)
• Female
• Humans
• Infant
• Infant, Newborn
• Infant, Newborn, Diseases (classification, diagnosis, genetics, therapy)
• Italy
• Male
• Mutation
• Potassium Channels, Inwardly Rectifying (genetics)
• Remission Induction (methods)
• Retrospective Studies
• Sulfonylurea Receptors (genetics)