MCID: DBT064
MIFTS: 45

Diabetes Mellitus, Transient Neonatal, 1

Categories: Genetic diseases, Rare diseases, Endocrine diseases, Metabolic diseases, Fetal diseases

Aliases & Classifications for Diabetes Mellitus, Transient Neonatal, 1

MalaCards integrated aliases for Diabetes Mellitus, Transient Neonatal, 1:

Name: Diabetes Mellitus, Transient Neonatal, 1 54 13 69
Transient Neonatal Diabetes Mellitus 12 50 56 29 14 69
Transient Neonatal Diabetes Mellitus 1 71 29
Diabetes Mellitus, Transient Neonatal 54 50
Tndm1 50 71
Tndm 50 56
Chromosome 6-Associated Transient Diabetes Mellitus 50
Diabetes Mellitus, 6q24-Related Transient Neonatal 50
Dmtn 50

Characteristics:

Orphanet epidemiological data:

56
transient neonatal diabetes mellitus
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: 1-9/1000000 (Europe); Age of onset: Antenatal,Neonatal;

OMIM:

54
Inheritance:
imprinted, paternally expressed gene on chromosome 6q22-q23


Classifications:

Orphanet: 56  
Rare endocrine diseases


Summaries for Diabetes Mellitus, Transient Neonatal, 1

OMIM : 54
Neonatal diabetes mellitus (NDM), defined as insulin-requiring hyperglycemia within the first month of life, is a rare entity, with an estimated incidence of 1 in 400,000 neonates (Shield, 2000). In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes (606176). In a significant number of patients with transient neonatal diabetes mellitus, type II diabetes appears later in life (Arthur et al., 1997). The major cause of transient neonatal diabetes (TND) is aberrant expression of imprinted genes at chromosome 6q24, associated in 20% of cases with DNA hypomethylation at the TND differentially methylated region (DMR), which lies within the imprinted promoter of the PLAGL1 gene (603044; Mackay et al., 2005). Over 50% of individuals with TND and hypomethylation at 6q24 also show mosaic DNA hypomethylation at other imprinted loci throughout the genome and a range of additional clinical features. (601410)

MalaCards based summary : Diabetes Mellitus, Transient Neonatal, 1, also known as transient neonatal diabetes mellitus, is related to diabetes mellitus, transient neonatal, 3 and diabetes mellitus, 6q24-related transient neonatal, and has symptoms including failure to thrive, hyperglycemia and intrauterine growth retardation. An important gene associated with Diabetes Mellitus, Transient Neonatal, 1 is ZFP57 (ZFP57 Zinc Finger Protein), and among its related pathways/superpathways are Type II diabetes mellitus and FOXA2 and FOXA3 transcription factor networks. The drugs Diazoxide and Antihypertensive Agents have been mentioned in the context of this disorder. Affiliated tissues include heart and pancreatic islet, and related phenotype is Increased shRNA abundance (Z-score > 2).

NIH Rare Diseases : 50 transient neonatal diabetes mellitus (tndb) is a type of diabetes that appears within the first few weeks of life but is transient; affected infants go into remission within a few months, with possible relapse to permanent diabetes in adolescence or adulthood. affected individuals have slow growth before birth followed by hyperglycemia, dehydration and failure to thrive in infancy. approximately 70% of cases are caused by the overactivity of certain genes in a region of the long (q) arm of chromosome 6 called 6q24. these cases are referred to as 6q24-related tndb; most (but not all) of these cases are not inherited. other genetic causes include mutations in the kcnj11 and abcc8 genes, which usually cause permanent neonatal diabetes. treatment may include rehydration and intravenous insulin at the time of diagnosis, followed by subcutaneous insulin. last updated: 8/28/2012

UniProtKB/Swiss-Prot : 71 Transient neonatal diabetes mellitus 1: Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first months of life. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes.

Disease Ontology : 12 A neonatal diabetes mellitus characterized by hyperglycemia during the neonatal period that remits during infancy but recurs in later life in most patients.

Related Diseases for Diabetes Mellitus, Transient Neonatal, 1

Diseases in the Neonatal Diabetes Mellitus family:

Diabetes Mellitus, Transient Neonatal, 1 Diabetes Mellitus, Transient Neonatal 2
Diabetes Mellitus, Transient Neonatal, 3 Diabetes Mellitus, 6q24-Related Transient Neonatal
Abcc8-Related Transient Neonatal Diabetes Mellitus 2 Diabetes Mellitus, Kcnj11-Related Transient Neonatal

Diseases related to Diabetes Mellitus, Transient Neonatal, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
id Related Disease Score Top Affiliating Genes
1 diabetes mellitus, transient neonatal, 3 34.4 ABCC8 KCNJ11
2 diabetes mellitus, 6q24-related transient neonatal 12.5
3 diabetes mellitus, transient neonatal 2 12.2
4 abcc8-related transient neonatal diabetes mellitus 2 12.1
5 prostate cancer 11.1
6 malaria 11.0
7 hypotrichosis 11.0
8 hereditary spherocytosis 10.9
9 paternal uniparental disomy of chromosome 21 10.8 HYMAI PLAGL1
10 writing disorder 10.7 ABCC8 KCNJ11
11 atrial fibrillation, familial, 12 10.7 ABCC8 KCNJ11
12 hemoglobin zurich 10.6 ABCC8 KCNJ11
13 noonan syndrome 2 10.5 ABCC8 KCNJ11
14 retinitis pigmentosa 68 10.5 ABCC8 INS
15 labyrinthine unilateral reactive loss 10.5 ABCC8 INS KCNJ11
16 acute insulin response 10.5 ABCC8 INS KCNJ11
17 morning glory syndrome 10.4 ABCC8 INS KCNJ11
18 inclusion body myopathy with paget disease of bone and frontotemporal dementia 10.4 ABCC8 INS KCNJ11
19 neurogenic arthropathy 10.4 ABCC8 INS KCNJ11
20 chondroma 10.4 ABCC8 INS KCNJ11
21 diabetic cataract 10.4 ABCC8 INS KCNJ11
22 breast abscess 10.4 GNAS-AS1 KCNQ1OT1
23 diaphanospondylodysostosis 10.4 ABCC8 INS KCNJ11
24 hypertrichosis 10.4 ABCC8 INS KCNJ11
25 exostosis 10.3 ABCC8 INS KCNJ11
26 triple x syndrome 10.3 ABCC8 INS KCNJ11
27 peroneal neuropathy 10.3 ABCC8 INS KCNJ11
28 multiple benign circumferential skin creases on limbs 10.3 KHDC3L NLRP7
29 trisomy 2 mosaicism 10.2 KHDC3L NLRP7
30 encephalopathy, progressive, with or without lipodystrophy 10.2 GRB10 KCNQ1OT1
31 neonatal diabetes mellitus 10.1
32 epileptic encephalopathy, early infantile, 8 10.1 KCNQ1OT1 MEST
33 deafness, autosomal recessive 18a 10.1 ABCC8 KCNJ11
34 congenital stationary night blindness 10.1 ABCC8 INS KCNJ11
35 limb-mammary syndrome 10.0 GRB10 INS
36 neuroblastoma 10.0
37 microcephaly, seizures, and developmental delay 10.0 KHDC3L NLRP7
38 placental site trophoblastic tumor 9.9 KHDC3L NLRP2 NLRP7
39 agnosia 9.9 KHDC3L NLRP2 NLRP7
40 paternal uniparental disomy of chromosome 6 9.9
41 aromatic l-amino acid decarboxylase deficiency 9.9 GRB10 KCNQ1OT1 MEST ZFP57
42 distal muscular dystrophy 9.8 ABCC8 HYMAI INS KCNJ11 PLAGL1 ZFP57
43 nephrolithiasis/osteoporosis, hypophosphatemic, 1 9.6 ABCC8 INS KCNQ1OT1 NLRP2 PLAGL1 ZFP57
44 nephronophthisis 19 4.8 ABCC8 DNMT3L FKBP6 GNAS-AS1 GRB10 HYMAI

Graphical network of the top 20 diseases related to Diabetes Mellitus, Transient Neonatal, 1:



Diseases related to Diabetes Mellitus, Transient Neonatal, 1

Symptoms & Phenotypes for Diabetes Mellitus, Transient Neonatal, 1

Symptoms via clinical synopsis from OMIM:

54

Lab:
hyperglycemia

Metabolic:
dehydration
insulin therapy usually required

Misc:
usual resolution within 6 months
late predisposition to type 2 (insulin resistant) diabetes

Growth:
intrauterine growth retardation
severe failure to thrive

Endocrine:
transient neonatal diabetes mellitus (tndm)


Clinical features from OMIM:

601410

Human phenotypes related to Diabetes Mellitus, Transient Neonatal, 1:

56 32 (show all 32)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 56 32 hallmark (90%) Very frequent (99-80%) HP:0001508
2 hyperglycemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0003074
3 intrauterine growth retardation 56 32 hallmark (90%) Very frequent (99-80%) HP:0001511
4 arthrogryposis multiplex congenita 56 32 frequent (33%) Frequent (79-30%) HP:0002804
5 global developmental delay 56 32 frequent (33%) Frequent (79-30%) HP:0001263
6 renal tubular dysfunction 56 32 occasional (7.5%) Occasional (29-5%) HP:0000124
7 coma 56 32 occasional (7.5%) Occasional (29-5%) HP:0001259
8 intellectual disability 56 32 frequent (33%) Frequent (79-30%) HP:0001249
9 motor delay 56 32 frequent (33%) Frequent (79-30%) HP:0001270
10 muscular hypotonia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001252
11 dehydration 56 32 hallmark (90%) Very frequent (99-80%) HP:0001944
12 ketonuria 56 32 frequent (33%) Frequent (79-30%) HP:0002919
13 weight loss 56 32 hallmark (90%) Very frequent (99-80%) HP:0001824
14 downturned corners of mouth 56 32 frequent (33%) Frequent (79-30%) HP:0002714
15 generalized tonic-clonic seizures 56 32 occasional (7.5%) Occasional (29-5%) HP:0002069
16 apraxia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002186
17 glycosuria 56 32 hallmark (90%) Very frequent (99-80%) HP:0003076
18 hearing impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0000365
19 steatorrhea 56 32 occasional (7.5%) Occasional (29-5%) HP:0002570
20 bilateral ptosis 56 32 frequent (33%) Frequent (79-30%) HP:0001488
21 prominent metopic ridge 56 32 frequent (33%) Frequent (79-30%) HP:0005487
22 generalized myoclonic seizures 56 32 occasional (7.5%) Occasional (29-5%) HP:0002123
23 hypovolemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0011106
24 abnormal heart morphology 56 32 occasional (7.5%) Occasional (29-5%) HP:0001627
25 transient neonatal diabetes mellitus 56 32 hallmark (90%) Very frequent (99-80%) HP:0008255
26 abnormality of the pancreatic islet cells 56 32 hallmark (90%) Very frequent (99-80%) HP:0006476
27 contractures of the joints of the lower limbs 56 32 frequent (33%) Frequent (79-30%) HP:0005750
28 seizures 56 Occasional (29-5%)
29 severe failure to thrive 32 HP:0001525
30 neurodevelopmental delay 56 Frequent (79-30%)
31 abnormality of the upper urinary tract 56 Occasional (29-5%)
32 autoimmune antibody positivity 56 Excluded (0%)

GenomeRNAi Phenotypes related to Diabetes Mellitus, Transient Neonatal, 1 according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.66 UROD
2 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.66 KCNJ11
3 Increased shRNA abundance (Z-score > 2) GR00366-A-124 9.66 KCNJ11
4 Increased shRNA abundance (Z-score > 2) GR00366-A-125 9.66 UROD KCNJ11 MEST
5 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.66 MEST
6 Increased shRNA abundance (Z-score > 2) GR00366-A-138 9.66 KCNJ11
7 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.66 MEST
8 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.66 MEST
9 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.66 UROD
10 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.66 KCNJ11
11 Increased shRNA abundance (Z-score > 2) GR00366-A-2 9.66 MEST
12 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.66 MEST
13 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.66 MEST
14 Increased shRNA abundance (Z-score > 2) GR00366-A-36 9.66 UROD
15 Increased shRNA abundance (Z-score > 2) GR00366-A-39 9.66 UROD
16 Increased shRNA abundance (Z-score > 2) GR00366-A-45 9.66 KCNJ11
17 Increased shRNA abundance (Z-score > 2) GR00366-A-51 9.66 KCNJ11
18 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.66 UROD
19 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.66 UROD
20 Increased shRNA abundance (Z-score > 2) GR00366-A-92 9.66 MEST

Drugs & Therapeutics for Diabetes Mellitus, Transient Neonatal, 1

Drugs for Diabetes Mellitus, Transient Neonatal, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Diazoxide Approved Phase 2, Phase 3 364-98-7 3019
2 Antihypertensive Agents Phase 2, Phase 3
3 Hypoglycemic Agents Phase 2, Phase 3
4 Vasodilator Agents Phase 2, Phase 3
5
Dinoprostone Approved 363-24-6 5280360
6
Oxytocin Approved, Vet_approved 50-56-6 439302 53477758
7
Benzocaine Approved 1994-09-7, 94-09-7 2337
8 tannic acid Approved, Nutraceutical
9 Neuroserpin
10 Astragalus Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Diazoxide In the Management Of Hypoglycemic Neonates Unknown status NCT00994149 Phase 2, Phase 3 Diazoxide;Ora-plus
2 Genetic Disease Gene Identification Unknown status NCT00916903
3 Gestational Diabetes: Induction Versus Expectant Management of Labour Completed NCT01058772
4 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168
5 Motivational Interviewing With Focus on Diet and Weight Gain in Pregnant Women With Type 2 Diabetes Recruiting NCT02883127

Search NIH Clinical Center for Diabetes Mellitus, Transient Neonatal, 1

Genetic Tests for Diabetes Mellitus, Transient Neonatal, 1

Genetic tests related to Diabetes Mellitus, Transient Neonatal, 1:

id Genetic test Affiliating Genes
1 Transient Neonatal Diabetes Mellitus 1 29
2 Transient Neonatal Diabetes Mellitus 29

Anatomical Context for Diabetes Mellitus, Transient Neonatal, 1

MalaCards organs/tissues related to Diabetes Mellitus, Transient Neonatal, 1:

39
Heart, Pancreatic Islet

Publications for Diabetes Mellitus, Transient Neonatal, 1

Variations for Diabetes Mellitus, Transient Neonatal, 1

UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Transient Neonatal, 1:

71
id Symbol AA change Variation ID SNP ID
1 ZFP57 p.Arg166His VAR_054771 rs199589695
2 ZFP57 p.His193Asn VAR_054772 rs78378398
3 ZFP57 p.His374Asp VAR_054773 rs79020217

ClinVar genetic disease variations for Diabetes Mellitus, Transient Neonatal, 1:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 ZFP57 NM_001109809.2(ZFP57): c.783C> A (p.Cys261Ter) single nucleotide variant Pathogenic rs61730328 GRCh37 Chromosome 6, 29641105: 29641105
2 ZFP57 NM_001109809.2(ZFP57): c.317_318delAG (p.Glu106Valfs) deletion Pathogenic rs606231121 GRCh38 Chromosome 6, 29675420: 29675421
3 ZFP57 NM_001109809.2(ZFP57): c.1383delC (p.Tyr462Ilefs) deletion Pathogenic rs606231122 GRCh38 Chromosome 6, 29672728: 29672728
4 ZFP57 NM_001109809.2(ZFP57): c.1372C> G (p.His458Asp) single nucleotide variant Pathogenic rs79020217 GRCh37 Chromosome 6, 29640516: 29640516
5 ZFP57 NM_001109809.2(ZFP57): c.743G> A (p.Arg248His) single nucleotide variant Pathogenic rs77625743 GRCh37 Chromosome 6, 29641145: 29641145
6 ZFP57 NM_001109809.2(ZFP57): c.829C> A (p.His277Asn) single nucleotide variant Pathogenic rs78378398 GRCh37 Chromosome 6, 29641059: 29641059
7 ZFP57 NM_001109809.2(ZFP57): c.898_905delACCCAGGC (p.Thr300Terfs) deletion Pathogenic rs606231123 GRCh37 Chromosome 6, 29640983: 29640990

Expression for Diabetes Mellitus, Transient Neonatal, 1

Search GEO for disease gene expression data for Diabetes Mellitus, Transient Neonatal, 1.

Pathways for Diabetes Mellitus, Transient Neonatal, 1

Pathways related to Diabetes Mellitus, Transient Neonatal, 1 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.11 ABCC8 INS KCNJ11
2 10.44 ABCC8 INS KCNJ11

GO Terms for Diabetes Mellitus, Transient Neonatal, 1

Cellular components related to Diabetes Mellitus, Transient Neonatal, 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 ATP-sensitive potassium channel complex GO:0008282 8.62 ABCC8 KCNJ11

Biological processes related to Diabetes Mellitus, Transient Neonatal, 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 negative regulation of insulin secretion GO:0046676 9.16 ABCC8 KCNJ11
2 DNA methylation involved in gamete generation GO:0043046 8.96 DNMT3L FKBP6
3 regulation of gene expression by genetic imprinting GO:0006349 8.62 DNMT3L ZFP57

Molecular functions related to Diabetes Mellitus, Transient Neonatal, 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 insulin receptor binding GO:0005158 8.96 GRB10 INS
2 ATP-activated inward rectifier potassium channel activity GO:0015272 8.62 ABCC8 KCNJ11

Sources for Diabetes Mellitus, Transient Neonatal, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....