Details of Disease

General Information of Disease (ID: DISFHF9K)

• Disease Name: Neonatal diabetes mellitus
• Synonyms: diabetes mellitus syndrome in newborn infant; congenital diabetes mellitus; NDM
• Definition: Neonatal diabetes mellitus presents as hyperglycemia, failure to thrive and, in some cases, dehydration and ketoacidosis which may be severe with coma, in a child within the first months of life.
• Disease Hierarchy:
  DISEB8Q0: Monogenic diabetes
  DISFHF9K: Neonatal diabetes mellitus
• Disease Identifiers:
  MONDO ID: MONDO_0016391
  UMLS CUI: C0158981
  MedGen ID: 57645
  Orphanet ID: 224
  SNOMED CT ID: 49817004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AGPAT2	TT9AYVR	Limited	Autosomal recessive	[1]
CD274	TTFAOU7	Limited	Autosomal recessive	[2]
ABCC8	TTP835K	moderate	Genetic Variation	[3]
PDX1	TT8SGZK	moderate	Genetic Variation	[4]
EIF2AK3	TT79U1M	Strong	Genetic Variation	[5]
FOXP3	TT1X3QF	Strong	Genetic Variation	[6]
GATA4	TT1VDN2	Strong	Autosomal dominant	[1]
GATA4	TT1VDN2	Strong	Biomarker	[7]
GCK	TTDLNGZ	Strong	Genetic Variation	[8]
HNF4A	TT2F3CD	Strong	Biomarker	[9]
IL2RA	TT10Y9E	Strong	Autosomal recessive	[1]
IL2RA	TT10Y9E	Strong	Biomarker	[10]
INS	TTZOPHG	Strong	Genetic Variation	[11]
SLC19A2	TT2A1DZ	Strong	Genetic Variation	[12]
STAT3	TTHJT3X	Strong	Genetic Variation	[13]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC2A2	DTUJPOL	Strong	Autosomal recessive	[1]
SLC2A2	DTUJPOL	Strong	Biomarker	[14]

This Disease Is Related to 21 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AGPAT2	OT5I4Y9K	Limited	Autosomal recessive	[1]
CD274	OTJ0VFDL	Limited	Autosomal recessive	[2]
GLIS3	OTBC960E	Limited	Genetic Variation	[15]
HNF1B	OTSYIC3T	Limited	Biomarker	[16]
PTF1A	OT7SWA57	Limited	Genetic Variation	[5]
TMEM167A	OT47KUOO	Limited	Autosomal recessive	[2]
GLIS2	OTOUUV1X	moderate	Genetic Variation	[17]
KLF11	OTKVQDJD	moderate	Genetic Variation	[18]
PDHX	OTG7O271	moderate	Genetic Variation	[19]
PHPT1	OTFYWNFX	moderate	Biomarker	[20]
RFX6	OT8H77DL	moderate	Genetic Variation	[21]
BSCL2	OT73V6Y4	Strong	Autosomal recessive	[1]
GATA4	OTQHWAZG	Strong	Autosomal dominant	[1]
GATA6	OTO2BC0F	Strong	Autosomal dominant	[1]
IER3IP1	OTCYSU28	Strong	Genetic Variation	[22]
IL2RA	OT0MWCHG	Strong	Autosomal recessive	[1]
MNX1	OTXP9FH1	Strong	Autosomal recessive	[1]
NEUROD1	OTZQ7QJ2	Strong	Genetic Variation	[23]
NEUROG3	OT6DIPWC	Strong	Genetic Variation	[24]
NKX2-2	OTDCOYNG	Strong	Autosomal recessive	[1]
SLC2A2	OTBL2W7R	Strong	Autosomal recessive	[1]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Functional characterization of activating mutations in the sulfonylurea receptor 1 (ABCC8) causing neonatal diabetes mellitus in Asian Indian children.Pediatr Diabetes. 2019 Jun;20(4):397-407. doi: 10.1111/pedi.12843. Epub 2019 Apr 2.
• [4] Biallelic PDX1 (insulin promoter factor 1) mutations causing neonatal diabetes without exocrine pancreatic insufficiency.Diabet Med. 2013 May;30(5):e197-200. doi: 10.1111/dme.12122. Epub 2013 Feb 28.
• [5] Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations.Eur J Endocrinol. 2015 Jun;172(6):697-705. doi: 10.1530/EJE-14-0852. Epub 2015 Mar 9.
• [6] Clinical heterogeneity in patients with FOXP3 mutations presenting with permanent neonatal diabetes.Diabetes Care. 2009 Jan;32(1):111-6. doi: 10.2337/dc08-1188. Epub 2008 Oct 17.
• [7] GATA4 mutations are a cause of neonatal and childhood-onset diabetes.Diabetes. 2014 Aug;63(8):2888-94. doi: 10.2337/db14-0061. Epub 2014 Apr 2.
• [8] Genetic mutations associated with neonatal diabetes mellitus in Omani patients.J Pediatr Endocrinol Metab. 2018 Jan 26;31(2):195-204. doi: 10.1515/jpem-2017-0284.
• [9] Precision medicine in type 2 diabetes.J Intern Med. 2019 Jan;285(1):40-48. doi: 10.1111/joim.12859. Epub 2018 Dec 7.
• [10] CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J Allergy Clin Immunol. 2007 Feb;119(2):482-7. doi: 10.1016/j.jaci.2006.10.007. Epub 2006 Dec 27.
• [11] A Novel c.125T>G (p.Val42Gly) Mutation in The Human INS Gene Leads to Neonatal Diabetes Mellitus via a Decrease in Insulin Synthesis.Exp Clin Endocrinol Diabetes. 2020 Mar;128(3):182-189. doi: 10.1055/a-0603-3463. Epub 2018 Jun 11.
• [12] Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia.Pediatr Diabetes. 2012 Jun;13(4):314-21. doi: 10.1111/j.1399-5448.2012.00855.x. Epub 2012 Feb 27.
• [13] An Activating STAT3 Mutation Causes Neonatal Diabetes through Premature Induction of Pancreatic Differentiation.Cell Rep. 2017 Apr 11;19(2):281-294. doi: 10.1016/j.celrep.2017.03.055.
• [14] Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia.Pediatr Diabetes. 2012 Sep;13(6):499-505. doi: 10.1111/j.1399-5448.2011.00828.x. Epub 2011 Nov 8.
• [15] Mutation screening of the GLIS3 gene in a cohort of 592 Chinese patients with congenital hypothyroidism.Clin Chim Acta. 2018 Jan;476:38-43. doi: 10.1016/j.cca.2017.11.011. Epub 2017 Nov 13.
• [16] Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia.Stem Cell Reports. 2016 Mar 8;6(3):357-67. doi: 10.1016/j.stemcr.2016.01.007. Epub 2016 Feb 11.
• [17] Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease.Vitam Horm. 2012;88:141-71. doi: 10.1016/B978-0-12-394622-5.00007-9.
• [18] Krppel-like factor-11, a transcription factor involved in diabetes mellitus, suppresses endothelial cell activation via the nuclear factor-B signaling pathway.Arterioscler Thromb Vasc Biol. 2012 Dec;32(12):2981-8. doi: 10.1161/ATVBAHA.112.300349. Epub 2012 Oct 4.
• [19] Pancreatic Duodenal Homeobox (PDX-1) in health and disease.J Pediatr Endocrinol Metab. 2002 Nov-Dec;15(9):1461-72. doi: 10.1515/jpem.2002.15.9.1461.
• [20] New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism.Eur J Endocrinol. 2010 Dec;163(6):953-62. doi: 10.1530/EJE-10-0435. Epub 2010 Sep 13.
• [21] Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus.Eur J Hum Genet. 2015 Dec;23(12):1744-8. doi: 10.1038/ejhg.2015.161. Epub 2015 Aug 12.
• [22] Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1: insights into the natural history of a rare disorder.Pediatr Diabetes. 2014 May;15(3):252-6. doi: 10.1111/pedi.12086. Epub 2013 Oct 21.
• [23] A homozygous missense mutation in NEUROD1 is associated with nonsyndromic autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014 Dec 4;56(1):150-5. doi: 10.1167/iovs.14-15382.
• [24] A novel NEUROG3 mutation in neonatal diabetes associated with a neuro-intestinal syndrome.Pediatr Diabetes. 2018 May;19(3):381-387. doi: 10.1111/pedi.12576. Epub 2017 Sep 22.