Transient neonatal diabetes mellitus caused by a novel mutation in the ABCC8 gene

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life.Case presentationWe report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up.ConclusionsThis report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

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An oral sulfonylurea in the treatment of transient neonatal diabetes mellitus

Clinical Therapeutics ◽

10.1016/j.clinthera.2009.04.003 ◽

2009 ◽

Vol 31 (4) ◽

pp. 816-820 ◽

Cited By ~ 10

Author(s):

Lindsey A. Loomba-Albrecht ◽

Nicole S. Glaser ◽

Dennis M. Styne ◽

Andrew A. Bremer

Keyword(s):

Diabetes Mellitus ◽

Neonatal Diabetes ◽

Neonatal Diabetes Mellitus ◽

Transient Neonatal Diabetes Mellitus ◽

Transient Neonatal Diabetes

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Differences between Transient Neonatal Diabetes Mellitus Subtypes can Guide Diagnosis and Therapy

Acta Endocrinologica ◽

10.1530/eje-20-1030 ◽

2021 ◽

Author(s):

Riccardo Bonfanti ◽

Dario Iafusco ◽

Ivana Rabbone ◽

Giacomo Diedenhofen ◽

Carla Bizzarri ◽

...

Keyword(s):

Diabetes Mellitus ◽

Clinical Features ◽

Umbilical Hernia ◽

Neonatal Diabetes ◽

Pharmacological Therapy ◽

Neonatal Diabetes Mellitus ◽

Data Set ◽

Transient Neonatal Diabetes Mellitus ◽

Remission Of Diabetes ◽

Transient Neonatal Diabetes

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 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.

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