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Pediatrics32 papers

Neonatal diabetes mellitus

Last edited: 4/14/2026

Overview

Neonatal diabetes mellitus (NDM) is a rare form of diabetes diagnosed in the first six months of life, characterized by hyperglycemia requiring insulin therapy. It can be transient or permanent, with genetic mutations playing a significant role in its etiology, particularly affecting pancreatic beta-cell function 112.

Diagnosis

  • Clinical Presentation: Hyperglycemia diagnosed within the first six months of life requiring insulin therapy 112.
  • Genetic Testing: Essential for identifying specific mutations (e.g., KCNJ11, ABCC8, SLC19A2, RFX6, GLIS3) 135818.
  • Additional Syndromic Features: Consider neurological features (developmental delay, epilepsy), congenital anomalies (hypothyroidism, glaucoma, intestinal atresias), and skeletal abnormalities 231820.
  • Initial Workup: Includes metabolic panel, thyroid function tests, and imaging for associated congenital anomalies 218.

    • Management

  • Permanent Neonatal Diabetes:
    • - Sulfonylureas: Transition to oral sulfonylureas (e.g., glyburide) in patients with KCNJ11 or ABCC8 mutations, particularly those without DEND syndrome 6711. - Thiamine Supplementation: For SLC19A2 mutations, thiamine may restore insulin production 5.
  • Transient Neonatal Diabetes: Often resolves spontaneously; monitoring and supportive care 12.
  • Insulin Therapy: Initial treatment for confirmed NDM until genetic testing and potential transition to alternative therapies 112.

    • Special Populations

  • Pediatrics: Focus on early genetic testing to guide treatment options (e.g., transitioning to sulfonylureas in appropriate cases) 6711.
  • Comorbidities: Manage associated conditions like congenital hypothyroidism, glaucoma, and skeletal abnormalities concurrently 218.

    • Key Recommendations

  • Genetic Testing: Perform comprehensive genetic testing to identify specific mutations guiding treatment decisions (e.g., KCNJ11, ABCC8, SLC19A2) 135818 (Evidence: Strong).
  • Consider Sulfonylurea Therapy: For patients with permanent neonatal diabetes due to KCNJ11 or ABCC8 mutations, evaluate transitioning to sulfonylureas to discontinue insulin 6711 (Evidence: Moderate).
  • Monitor for Syndromic Features: Screen for associated neurological and congenital anomalies to tailor comprehensive management plans 231820 (Evidence: Moderate).

    • References

    1 Donis R, Patel KA, Wakeling MN, Johnson MB, Amoli MM, Yildiz M et al.. A homozygous TARS2 variant is a novel cause of syndromic neonatal diabetes. Diabetic medicine : a journal of the British Diabetic Association 2025. link 2 Sarıkaya E, Kendirci M, Demir M, Dündar M. Neonatal Diabetes, Congenital Hypothyroidism, and Congenital Glaucoma Coexistence: A Case of . Journal of clinical research in pediatric endocrinology 2023. link 3 Yagasaki H, Sano F, Narusawa H, Watanabe D, Kaga Y, Kobayashi K et al.. Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome. American journal of medical genetics. Part A 2022. link 4 Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E et al.. Genotype and Phenotype Heterogeneity in Neonatal Diabetes: A Single Centre Experience in Turkey. Journal of clinical research in pediatric endocrinology 2021. link 5 Sun C, Pei Z, Zhang M, Sun B, Yang L, Zhao Z et al.. Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation. Journal of diabetes 2018. link 6 Ozsu E, Giri D, Seymen Karabulut G, Senniappan S. Successful transition to sulfonylurea therapy in two Iraqi siblings with neonatal diabetes mellitus and iDEND syndrome due to ABCC8 mutation. Journal of pediatric endocrinology & metabolism : JPEM 2016. link 7 Peña-Almazan S. Successful transition to sulfonylurea in neonatal diabetes, developmental delay, and seizures (DEND syndrome) due to R50P KCNJ11 mutation. Diabetes research and clinical practice 2015. link 8 Shaw-Smith C, Flanagan SE, Patch AM, Grulich-Henn J, Habeb AM, Hussain K et al.. Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. Pediatric diabetes 2012. link 9 Spiegel R, Dobbie A, Hartman C, de Vries L, Ellard S, Shalev SA. Clinical characterization of a newly described neonatal diabetes syndrome caused by RFX6 mutations. American journal of medical genetics. Part A 2011. link 10 Clark RH, McTaggart JS, Webster R, Mannikko R, Iberl M, Sim XL et al.. Muscle dysfunction caused by a KATP channel mutation in neonatal diabetes is neuronal in origin. Science (New York, N.Y.) 2010. link 11 Mohamadi A, Clark LM, Lipkin PH, Mahone EM, Wodka EL, Plotnick LP. Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15-yr-old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM. Pediatric diabetes 2010. link 12 Greeley SA, Tucker SE, Worrell HI, Skowron KB, Bell GI, Philipson LH. Update in neonatal diabetes. Current opinion in endocrinology, diabetes, and obesity 2010. link 13 Rubio-Cabezas O, Patch AM, Minton JA, Flanagan SE, Edghill EL, Hussain K et al.. Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. The Journal of clinical endocrinology and metabolism 2009. link 14 Winkler M, Lutz R, Russ U, Quast U, Bryan J. Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. The Journal of biological chemistry 2009. link 15 Chappell L, Gorman S, Campbell F, Ellard S, Rice G, Dobbie A et al.. A further example of a distinctive autosomal recessive syndrome comprising neonatal diabetes mellitus, intestinal atresias and gall bladder agenesis. American journal of medical genetics. Part A 2008. link 16 Shield JP. Neonatal diabetes. Hormone research 2007. link 17 Masia R, Koster JC, Tumini S, Chiarelli F, Colombo C, Nichols CG et al.. An ATP-binding mutation (G334D) in KCNJ11 is associated with a sulfonylurea-insensitive form of developmental delay, epilepsy, and neonatal diabetes. Diabetes 2007. link 18 Senée V, Chelala C, Duchatelet S, Feng D, Blanc H, Cossec JC et al.. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nature genetics 2006. link 19 Goksen D, Darcan S, Coker M, Aksu G, Yildiz B, Kara S et al.. Permanent neonatal diabetes with arthrogryposis multiplex congenita and neurogenic bladder - a new syndrome?. Pediatric diabetes 2006. link 20 Gloyn AL, Diatloff-Zito C, Edghill EL, Bellanné-Chantelot C, Nivot S, Coutant R et al.. KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. European journal of human genetics : EJHG 2006. link 21 Hoveyda N, Shield JP, Garrett C, Chong WK, Beardsall K, Bentsi-Enchill E et al.. Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome. Journal of medical genetics 1999. link 22 von Mühlendahl KE, Herkenhoff H. Long-term course of neonatal diabetes. The New England journal of medicine 1995. link

    Original source

    1. [1]
      A homozygous TARS2 variant is a novel cause of syndromic neonatal diabetes. — Donis R, Patel KA, Wakeling MN, Johnson MB, Amoli MM, Yildiz M et al. Diabetic medicine : a journal of the British Diabetic Association (2025)
    2. [2]
      Neonatal Diabetes, Congenital Hypothyroidism, and Congenital Glaucoma Coexistence: A Case of — Sarıkaya E, Kendirci M, Demir M, Dündar M Journal of clinical research in pediatric endocrinology (2023)
    3. [3]
      Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome. — Yagasaki H, Sano F, Narusawa H, Watanabe D, Kaga Y, Kobayashi K et al. American journal of medical genetics. Part A (2022)
    4. [4]
      Genotype and Phenotype Heterogeneity in Neonatal Diabetes: A Single Centre Experience in Turkey. — Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E et al. Journal of clinical research in pediatric endocrinology (2021)
    5. [5]
      Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation. — Sun C, Pei Z, Zhang M, Sun B, Yang L, Zhao Z et al. Journal of diabetes (2018)
    6. [6]
      Successful transition to sulfonylurea therapy in two Iraqi siblings with neonatal diabetes mellitus and iDEND syndrome due to ABCC8 mutation. — Ozsu E, Giri D, Seymen Karabulut G, Senniappan S Journal of pediatric endocrinology & metabolism : JPEM (2016)
    7. [7]
      Successful transition to sulfonylurea in neonatal diabetes, developmental delay, and seizures (DEND syndrome) due to R50P KCNJ11 mutation. — Peña-Almazan S Diabetes research and clinical practice (2015)
    8. [8]
      Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. — Shaw-Smith C, Flanagan SE, Patch AM, Grulich-Henn J, Habeb AM, Hussain K et al. Pediatric diabetes (2012)
    9. [9]
      Clinical characterization of a newly described neonatal diabetes syndrome caused by RFX6 mutations. — Spiegel R, Dobbie A, Hartman C, de Vries L, Ellard S, Shalev SA American journal of medical genetics. Part A (2011)
    10. [10]
      Muscle dysfunction caused by a KATP channel mutation in neonatal diabetes is neuronal in origin. — Clark RH, McTaggart JS, Webster R, Mannikko R, Iberl M, Sim XL et al. Science (New York, N.Y.) (2010)
    11. [11]
      Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15-yr-old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM. — Mohamadi A, Clark LM, Lipkin PH, Mahone EM, Wodka EL, Plotnick LP Pediatric diabetes (2010)
    12. [12]
      Update in neonatal diabetes. — Greeley SA, Tucker SE, Worrell HI, Skowron KB, Bell GI, Philipson LH Current opinion in endocrinology, diabetes, and obesity (2010)
    13. [13]
      Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. — Rubio-Cabezas O, Patch AM, Minton JA, Flanagan SE, Edghill EL, Hussain K et al. The Journal of clinical endocrinology and metabolism (2009)
    14. [14]
      Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. — Winkler M, Lutz R, Russ U, Quast U, Bryan J The Journal of biological chemistry (2009)
    15. [15]
      A further example of a distinctive autosomal recessive syndrome comprising neonatal diabetes mellitus, intestinal atresias and gall bladder agenesis. — Chappell L, Gorman S, Campbell F, Ellard S, Rice G, Dobbie A et al. American journal of medical genetics. Part A (2008)
    16. [16]
      Neonatal diabetes. — Shield JP Hormone research (2007)
    17. [17]
      An ATP-binding mutation (G334D) in KCNJ11 is associated with a sulfonylurea-insensitive form of developmental delay, epilepsy, and neonatal diabetes. — Masia R, Koster JC, Tumini S, Chiarelli F, Colombo C, Nichols CG et al. Diabetes (2007)
    18. [18]
      Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. — Senée V, Chelala C, Duchatelet S, Feng D, Blanc H, Cossec JC et al. Nature genetics (2006)
    19. [19]
      Permanent neonatal diabetes with arthrogryposis multiplex congenita and neurogenic bladder - a new syndrome? — Goksen D, Darcan S, Coker M, Aksu G, Yildiz B, Kara S et al. Pediatric diabetes (2006)
    20. [20]
      KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. — Gloyn AL, Diatloff-Zito C, Edghill EL, Bellanné-Chantelot C, Nivot S, Coutant R et al. European journal of human genetics : EJHG (2006)
    21. [21]
      Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome. — Hoveyda N, Shield JP, Garrett C, Chong WK, Beardsall K, Bentsi-Enchill E et al. Journal of medical genetics (1999)
    22. [22]
      Long-term course of neonatal diabetes. — von Mühlendahl KE, Herkenhoff H The New England journal of medicine (1995)
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