Transient Neonatal Diabetes Mellitus and Seizure with an Unknown Etiology

AbstractNeonatal diabetes mellitus (NDM) is a monogenic form of diabetes, usually occurring in the first 6 months of life. Here, we present a newborn, which was admitted with epileptic seizure on the postnatal second day of life. Sepsis and meningitis were ruled out. Cranial imaging and electroencephalography revealed normal. She developed transient NDM on the follow-up and was diagnosed to carry an ABCC8 mutation. Although the neurological features are more common in patients with KCJN11 mutations, patients with ABCC8 mutations could also represent with subtle neurodevelopmental changes or even with epileptic seizures. The genetic testing and appropriate therapy is important in this patient group for predicting clinical course and possible additional features.

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Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes

Acta Endocrinologica ◽

10.1530/eje-12-0227 ◽

2012 ◽

Vol 167 (3) ◽

pp. 417-421 ◽

Cited By ~ 3

Author(s):

Clementine S Fraser ◽

Oscar Rubio-Cabezas ◽

Jennifer A Littlechild ◽

Sian Ellard ◽

Andrew T Hattersley ◽

...

Keyword(s):

Diabetes Mellitus ◽

Amino Acid ◽

Neonatal Diabetes ◽

Neurological Status ◽

Neonatal Diabetes Mellitus ◽

Wild Type ◽

Amino Acid Properties ◽

Transient Neonatal Diabetes ◽

Neurological Features ◽

The Difference

BackgroundMutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the β-cell KATP channel, are a common cause of neonatal diabetes. The diabetes may be permanent neonatal diabetes mellitus (PNDM) or transient neonatal diabetes mellitus (TNDM), and in ∼20% of patients, neurological features are observed. A correlation between the position of the mutation in the protein and the clinical phenotype has previously been described; however, recently, this association has become less distinct with different mutations at the same residues now reported in patients with different diabetic and/or neurological phenotypes.MethodsWe identified from the literature, and our unpublished series, KCNJ11 mutations that affected residues harbouring various amino acid substitutions (AAS) causing differences in diabetic or neurological status. Using the Grantham amino acid scoring system, we investigated whether the difference in properties between the wild-type and the different AAS at the same residue could predict phenotypic severity.ResultsPair-wise analysis demonstrated higher Grantham scores for mutations causing PNDM or diabetes with neurological features when compared with mutations affecting the same residue that causes TNDM (P=0.013) or diabetes without neurological features (P=0.016) respectively. In just five of the 25 pair-wise analyses, a lower Grantham score was observed for the more severe phenotype. In each case, the wild-type residue was glycine, the simplest amino acid.ConclusionThis study demonstrates the importance of the specific AAS in determining phenotype and highlights the potential utility of the Grantham score for predicting phenotypic severity for novel KCNJ11 mutations affecting previously mutated residues.

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The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0030 ◽

2020 ◽

Vol 33 (12) ◽

pp. 1605-1608

Author(s):

Xiao Qin ◽

Jingzi Zhong ◽

Dan Lan

Keyword(s):

Diabetes Mellitus ◽

Novel Mutation ◽

Male Infant ◽

Neonatal Diabetes ◽

Monogenic Diabetes ◽

Neonatal Diabetes Mellitus ◽

Rare Form ◽

Case Presentation ◽

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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