PNDM
MCID: PRM030
MIFTS: 48

Permanent Neonatal Diabetes Mellitus (PNDM) malady

Neuronal, Endocrine categories

Summaries for Permanent Neonatal Diabetes Mellitus

Sources:
21Genetics Home Reference, 43NIH Rare Diseases, 64Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
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NIH Rare Diseases:43 Permanent neonatal diabetes mellitus (pndb) is a type of diabetes that appears within the first 6 months of life and persists throughout life. affected individuals have slow growth before birth followed by hyperglycemia, dehydration and failure to thrive in infancy. some individuals also have neurological problems including developmental delay and epilepsy; when these problems are present with pndb, it is called dend syndrome. a few individuals with pndb also have an underdeveloped pancreas and may have digestive problems. pndb is caused by mutations in any one of several genes (some of which have not yet been identified) including the kcnj11, abcc8, and ins genes. it may be inherited in an autosomal recessive or autosomal dominant manner. treatment includes rehydration, insulin therapy and/or long-term therapy with oral sulfonylureas (in some cases). last updated: 8/24/2012

MalaCards: Permanent Neonatal Diabetes Mellitus, also known as PNDM, is related to neonatal diabetes mellitus and pancreatic agenesis. An important gene associated with Permanent Neonatal Diabetes Mellitus is GCK (glucokinase (hexokinase 4)), and among its related pathways are Hepatic ABC Transporters and Development Leptin signaling via PI3K-dependent pathway. The compounds chromium picolinate and meglitinide have been mentioned in the context of this disorder. Affiliated tissues include pancreas, and related mouse phenotypes are no phenotypic analysis and endocrine/exocrine gland.

Genetics Home Reference:21 Permanent neonatal diabetes mellitus is a type of diabetes that first appears within the first 6 months of life and persists throughout the lifespan. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy.

Wikipedia:64 A newly identified and potentially treatable form of monogenic diabetes is the neonatal diabetes caused... more...

Description from OMIM:47 606176

GeneReviews summary for dmn

Aliases & Classifications for Permanent Neonatal Diabetes Mellitus

Sources:
19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 47OMIM, 49Orphanet, 61UMLS, 26ICD10 via Orphanet
See all sources

Classifications:

Malacards categories (disease lists): (See all malacards categories)
Anatomical: Neuronal, Endocrine


Characteristics (Orphanet epidemiological data):

49
developmental delay - epilepsy - neonatal diabetes:
Inheritance: Autosomal dominant,Sporadic; Prevalence: <1/1000000; Age of onset: Neonatal/infancy
permanent neonatal diabetes mellitus:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/1000000; Age of onset: Neonatal/infancy


Aliases & Descriptions:

permanent neonatal diabetes mellitus 19 43 20 22 21 49
pndm 43 21 49
permanent diabetes mellitus of infancy 19 43
diabetes mellitus, permanent neonatal 47 61
developmental delay, epilepsy, and neonatal diabetes 61
developmental delay - epilepsy - neonatal diabetes 49
dend syndrome 49


External Ids:

OMIM47 606176
ICD10 via Orphanet26 P70.2

Related Diseases for Permanent Neonatal Diabetes Mellitus

Sources:
17GeneCards, 18GeneDecks
See all sources

Diseases in the Permanent Neonatal Diabetes Mellitus family:

diabetes mellitus, permanent neonatal, with cerebellar agenesis diabetes mellitus, permanent neonatal, with neurologic features

Diseases related to Permanent Neonatal Diabetes Mellitus via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 47)
idRelated DiseaseScoreTop Affiliating Genes
1neonatal diabetes mellitus31.5GCK, KCNJ5, KCNJ11, PDX1, ABCC8, INS
2pancreatic agenesis30.6PDX1
3diabetes, permanent neonatal11.0
4n syndrome10.5
5intermediate dend syndrome10.4
6transient neonatal diabetes mellitus10.4
7abcc8-related permanent neonatal diabetes mellitus10.4
8gck-related permanent neonatal diabetes mellitus10.4
9kcnj11-related permanent neonatal diabetes mellitus10.4
10pdx1-related permanent neonatal diabetes mellitus10.4
11ins-related permanent neonatal diabetes mellitus10.4
12diabetes mellitus, permanent neonatal, with neurologic features10.4
13diabetic ketoacidosis10.3
14exocrine pancreatic insufficiency10.3
15diabetes mellitus, permanent neonatal, with cerebellar agenesis10.3
16glucagonoma10.0PDX1
17beckwith-wiedemann syndrome10.0ABCC8
18essential hypertension10.0INS
19pancreatitis10.0INS
20pituitary adenoma10.0ABCC8
21hypokalemia10.0INS
22hyperaldosteronism10.0KCNJ5
23lymphopenia10.0IDDM2
24coronary heart disease10.0INS
25acute myocardial infarction10.0KCNJ5
26hyperinsulinemic hypoglycemia10.0INS, ABCC8
27type 1 diabetes10.0INS, GCK
28hypertension10.0INS
29familial hyperinsulinism10.0KCNJ11, GCK, ABCC8
30myocardial infarction10.0KCNJ5, PDX1
31hyperammonemia multi-gene panels10.0KCNJ11, ABCC8, GCK
32hyperuricemia10.0GCK, INS
33insulin resistance10.0GCK, ABCC8, INS
34metabolic syndrome x10.0INS, ABCC8, GCK
35adenoma10.0INS, KCNJ5
36epilepsy syndrome10.0ABCC8, KCNJ11, KCNJ5
37ischemia10.0KCNJ5, GCK, ABCC8
38maturity-onset diabetes of the young10.0GCK, KCNJ11, PDX1, INS
39gestational diabetes10.0ABCC8, KCNJ11, GCK, INS
40glucose intolerance10.0KCNJ11, INS, ABCC8, GCK
41hyperglycemia10.0PDX1, ABCC8, GCK, KCNJ11, INS
42hypoglycemia10.0GCK, KCNJ5, INS, ABCC8, KCNJ11
43hyperinsulinism10.0ABCC8, KCNJ5, KCNJ11, INS, GCK
44obesity10.0KCNJ5, KCNJ11, GCK, ABCC8, INS
45insulinoma9.9GCK, KCNJ5, INS, ABCC8, PDX1, KCNJ11
46diabetes mellitus9.9GCK, KCNJ11, PDX1, INS, ABCC8, KCNJ5
47type 2 diabetes mellitus9.9ABCC8, KCNJ5, KCNJ11, PDX1, IDDM2, GCK

Graphical network of the top 20 diseases related to Permanent Neonatal Diabetes Mellitus:



Diseases related to permanent neonatal diabetes mellitus

Clinical Features for Permanent Neonatal Diabetes Mellitus

Sources:
47OMIM
See all sources

Clinical features from OMIM:

606176

Clinical synopsis from OMIM:

606176

Drugs & Therapeutics for Permanent Neonatal Diabetes Mellitus

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials
See all sources

Approved drugs:

Search CenterWatch for Permanent Neonatal Diabetes Mellitus

Drug clinical trials:

Search ClinicalTrials for Permanent Neonatal Diabetes Mellitus

Search NIH Clinical Center for Permanent Neonatal Diabetes Mellitus

Search CenterWatch for Permanent Neonatal Diabetes Mellitus

Genetic Tests for Permanent Neonatal Diabetes Mellitus

Sources:
20GeneTests, 22GTR
See all sources

Genetic tests related to Permanent Neonatal Diabetes Mellitus:

id Genetic test Affiliating Genes
1 Permanent Neonatal Diabetes Mellitus20 22 PDX1

Anatomical Context for Permanent Neonatal Diabetes Mellitus

Sources:
33MalaCards
See all sources

MalaCards organs/tissues related to Permanent Neonatal Diabetes Mellitus:

33
Pancreas

Animal Models for Permanent Neonatal Diabetes Mellitus or affiliated genes

Sources:
37MGI, 28inGenious Targeting Laboratory
See all sources

MGI Mouse Phenotypes related to Permanent Neonatal Diabetes Mellitus:

37
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00030128.2ABCC8, INS, PDX1, KCNJ11
2MP:00053797.5ABCC8, INS, PDX1, GCK, KCNJ11

Publications for Permanent Neonatal Diabetes Mellitus

Sources:
51PubMed
See all sources

Articles related to Permanent Neonatal Diabetes Mellitus:

(show all 38)
idTitleAuthorsYear
1
Permanent neonatal diabetes mellitus in monozygotic twins achieving low-dose sulfonylurea therapy. (23959658)
2014
2
Unsuccessful switch from insulin to sulfonylurea therapy in permanent neonatal diabetes mellitus due to an R201H mutation in the KCNJ11 gene: a case report. (23434183)
2013
3
Permanent neonatal diabetes mellitus: prevalence and genetic diagnosis in the SEARCH for Diabetes in Youth Study. (23050777)
2013
4
Changing the Treatment of Permanent Neonatal Diabetes Mellitus from Insulin to Glibenclamide in a 4-Month-Old Infant with KCNJ11 Activating Mutation. (24130952)
2013
5
EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome. (24168455)
2013
6
Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene. (24150202)
2013
7
Three cases of permanent neonatal diabetes mellitus: genotypes and management outcome. (22815030)
2012
8
Permanent neonatal diabetes mellitus. (23569512)
2012
9
Personalized medicine switching from insulin to sulfonylurea in permanent neonatal diabetes mellitus dictated by a novel activating ABCC8 mutation. (22306677)
2012
10
Early-onset, severe lipoatrophy in a patient with permanent neonatal diabetes mellitus secondary to a recessive mutation in the INS gene. (21910811)
2012
11
Permanent neonatal diabetes mellitus: same mutation, different glycemic control with sulfonylurea therapy on long-term follow-up. (22672870)
2012
12
Permanent neonatal diabetes mellitus due to KCNJ11 mutation in a Portuguese family: transition from insulin to oral sulfonylureas. (22768671)
2012
13
Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia. (22060631)
2012
14
A new variant of a known mutation in two siblings with permanent neonatal diabetes mellitus. (21823539)
2011
15
Permanent neonatal diabetes mellitus--the importance of diabetes differential diagnosis in neonates and infants. (21054355)
2011
16
Four novel cases of permanent neonatal diabetes mellitus caused by homozygous mutations in the glucokinase gene. (21518409)
2011
17
KCNJ11 activating mutations cause both transient and permanent neonatal diabetes mellitus in Cypriot patients. (21352428)
2011
18
The first case report of sulfonylurea use in a woman with permanent neonatal diabetes mellitus due to KCNJ11 mutation during a high-risk pregnancy. (20466780)
2010
19
Transfer from insulin to sulfonylurea treatment in a chinese patient with permanent neonatal diabetes mellitus due to a KCNJ11 R201H mutation. (19247925)
2009
20
Improved diabetic control during oral sulfonylurea treatment in two children with permanent neonatal diabetes mellitus. (19774848)
2009
21
Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. (18451997)
2008
22
Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene. (19169493)
2008
23
Permanent neonatal diabetes mellitus caused by a novel homozygous (T168A) glucokinase (GCK) mutation: initial response to oral sulphonylurea therapy. (18571549)
2008
24
Permanent neonatal diabetes mellitus due to a C96Y heterozygous mutation in the insulin gene. A case report. (18981553)
2008
25
Sulphonylurea treatment does not improve psychomotor development in children with KCNJ11 mutations causing permanent neonatal diabetes mellitus accompanied by developmental delay and epilepsy (DEND syndrome). (17888143)
2007
26
A mutation in the TMD0-L0 region of sulfonylurea receptor-1 (L225P) causes permanent neonatal diabetes mellitus (PNDM). (17317760)
2007
27
Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2. (17491708)
2006
28
Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene. (16816952)
2006
29
Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2. (15531505)
2004
30
Permanent neonatal diabetes mellitus manifesting as diabetic ketoacidosis. (14976569)
2003
31
Neonatal diabetes mellitus: chromosomal analysis in transient and permanent cases. (12378186)
2002
32
Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6. (10617703)
2000
33
Permanent neonatal diabetes mellitus: clinical presentation and epidemiology in Oman. (10212083)
1999
34
Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth. (10798084)
1999
35
Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis. (8506821)
1993
36
Permanent Neonatal Diabetes Mellitus (20301620)
1993
37
Permanent neonatal diabetes mellitus: lack of diabetic complications after a 20-year follow up. (1537364)
1992
38
Permanent neonatal diabetes mellitus: a case report with plasma insulin studies. (1130120)
1975

Genetic Variations for Permanent Neonatal Diabetes Mellitus

Sources:
63UniProtKB/Swiss-Prot
See all sources

Genetic disease variations for Permanent Neonatal Diabetes Mellitus:

63 (show all 41)
id Symbol AA change Variation SNP ID
1ABCC8p.Phe132LeuVAR_029778
2ABCC8p.Leu213ArgVAR_029779
3ABCC8p.Ile1424ValVAR_029787
4ABCC8p.Val86AlaVAR_031354
5INSp.Ala24AspVAR_063723rs80356663
6INSp.His29AspVAR_063724rs121908272
7INSp.Gly32ArgVAR_063725rs80356664
8INSp.Gly32SerVAR_063726rs80356664
9INSp.Leu35ProVAR_063727rs121908273
10INSp.Cys43GlyVAR_063728rs80356666
11INSp.Gly47ValVAR_063730rs80356667
12INSp.Phe48CysVAR_063731rs80356668
13INSp.Arg89CysVAR_063735rs80356669
14INSp.Gly90CysVAR_063736rs80356670
15INSp.Cys96SerVAR_063737rs80356671
16INSp.Cys96TyrVAR_063738rs80356671
17INSp.Ser101CysVAR_063739rs121908276
18INSp.Tyr103CysVAR_063740rs121908277
19INSp.Tyr108CysVAR_063741rs80356672
20KCNJ11p.Phe35LeuVAR_026498
21KCNJ11p.Phe35ValVAR_026499
22KCNJ11p.Arg50ProVAR_026500
23KCNJ11p.Gln52ArgVAR_026501
24KCNJ11p.Val59GlyVAR_026504
25KCNJ11p.Val59MetVAR_026505
26KCNJ11p.Lys170AsnVAR_026508
27KCNJ11p.Lys170ArgVAR_026509
28KCNJ11p.Arg201CysVAR_026511
29KCNJ11p.Arg201HisVAR_026512
30KCNJ11p.Ile296LeuVAR_026514
31KCNJ11p.Glu322LysVAR_026515
32KCNJ11p.Tyr330CysVAR_026516
33KCNJ11p.Phe333IleVAR_026517
34KCNJ11p.His46TyrVAR_031332
35KCNJ11p.Arg50GlnVAR_031333
36KCNJ11p.Gly53AspVAR_031334
37KCNJ11p.Leu164ProVAR_031341
38KCNJ11p.Cys166TyrVAR_031342
39KCNJ11p.Lys170ThrVAR_031343
40KCNJ11p.Arg201LeuVAR_031344
41KCNJ11p.Tyr330SerVAR_031348

Expression for genes affiliated with Permanent Neonatal Diabetes Mellitus

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
Expression patterns in normal tissues for genes affiliated with Permanent Neonatal Diabetes Mellitus

Search GEO for disease gene expression data for Permanent Neonatal Diabetes Mellitus.

Pathways for genes affiliated with Permanent Neonatal Diabetes Mellitus

Sources:
52QIAGEN, 12EMD Millipore, 54Reactome, 50PharmGKB, 30KEGG, 38NCBI BioSystems Database
See all sources

Pathways related to Permanent Neonatal Diabetes Mellitus according to GeneCards/GeneDecks:

(show all 14)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Hide members
9.6INS, GCK
2
Development Leptin signaling via PI3K-dependent pathway
Hide members
9.4ABCC8, KCNJ11
39.4ABCC8, KCNJ11
49.3KCNJ5, KCNJ11
59.2PDX1, INS
6
Hide members
9.0KCNJ11, INS, ABCC8
78.9KCNJ5, KCNJ11, ABCC8
8
Hide members
8.9ABCC8, KCNJ11, KCNJ5
98.9KCNJ11, KCNJ5, ABCC8
10
Hide members
8.9ABCC8, KCNJ11, KCNJ5
11
Hide members
8.8GCK, INS, PDX1
127.8ABCC8, KCNJ11, GCK, PDX1, INS
13
Hide members
7.8GCK, INS, ABCC8, KCNJ11, PDX1
147.8KCNJ11, GCK, PDX1, INS, ABCC8

Compounds for genes affiliated with Permanent Neonatal Diabetes Mellitus

Sources:
45Novoseek, 11DrugBank, 29IUPHAR, 24HMDB, 60Tocris Bioscience, 50PharmGKB
See all sources

Compounds related to Permanent Neonatal Diabetes Mellitus according to GeneCards/GeneDecks:

(show top 50)    (show all 53)
idCompoundScoreTop Affiliating Genes
1chromium picolinate4510.0INS, GCK
2meglitinide4510.0ABCC8, INS
3mitiglinide45 1111.0INS, ABCC8
4minoxidil45 29 1112.0KCNJ5, ABCC8
5chlorpropamide45 1110.9ABCC8, INS
6benzopyran459.9KCNJ5, ABCC8
7dicyandiamide459.9ABCC8, KCNJ5
8pinacidil459.9KCNJ5, ABCC8
9cibenzoline459.8KCNJ11, ABCC8
10aicar45 11 2411.8INS, GCK
11phentolamine29 45 1111.8KCNJ5, ABCC8
12levosimendan45 1110.7KCNJ11, KCNJ5
13p1075609.6KCNJ5, KCNJ11
14levcromakalim609.6KCNJ5, KCNJ11
15tertiapin-q609.6KCNJ5, KCNJ11
16proglucagon459.5GCK, PDX1
17glipizide45 1110.5ABCC8, INS, KCNJ5
18nateglinide45 50 1111.5KCNJ5, INS, ABCC8
19glycogen45 2410.4ABCC8, INS, GCK
20gliclazide45 50 1111.4KCNJ11, INS, ABCC8
21nicorandil45 2910.4KCNJ5, KCNJ11, ABCC8
22mgadp459.4ABCC8, KCNJ11, KCNJ5
23cromakalim45 2910.3ABCC8, KCNJ11, KCNJ5
24Glyburide119.3ABCC8, KCNJ11, KCNJ5
25nicotinamide45 1110.3INS, PDX1
26preproinsulin459.2GCK, PDX1, INS
27i-app459.2INS, PDX1, GCK
28fatty acid459.2ABCC8, INS, GCK
29incretin459.2GCK, PDX1, INS
30streptozotocin459.2INS, PDX1, GCK
31lactate459.1INS, GCK, KCNJ5
32metformin45 50 1111.0KCNJ11, GCK, INS, ABCC8
33repaglinide45 50 1110.9KCNJ5, KCNJ11, INS, ABCC8
34glimepiride45 50 1110.9ABCC8, INS, KCNJ11, KCNJ5
35glibenclamide45 29 50 6011.9KCNJ5, KCNJ11, INS, ABCC8
36potassium45 11 2410.9KCNJ5, KCNJ11, GCK, ABCC8
37magnesium45 11 2410.9KCNJ5, KCNJ11, GCK, ABCC8
38arginine458.9ABCC8, INS, GCK, KCNJ11
39lysine458.8KCNJ5, KCNJ11, ABCC8
40adp45 29 2410.8KCNJ5, KCNJ11, GCK, ABCC8
41atp45 299.7KCNJ5, KCNJ11, GCK, ABCC8
42c-peptide458.6KCNJ11, GCK, PDX1, INS
43diazoxide45 60 29 1111.5KCNJ5, KCNJ11, GCK, INS, ABCC8
44tolbutamide45 50 29 1111.5KCNJ5, KCNJ11, GCK, INS, ABCC8
45glutamate458.5KCNJ5, KCNJ11, GCK, INS, ABCC8
46lipid458.4ABCC8, INS, GCK, KCNJ5
47calcium45 50 11 2410.8KCNJ5, KCNJ11, GCK, PDX1, ABCC8
48katp457.7ABCC8, KCNJ5, KCNJ11, GCK, PDX1, INS
49sulfonylurea457.7KCNJ5, KCNJ11, GCK, PDX1, INS, ABCC8
50glucose457.7KCNJ5, KCNJ11, GCK, PDX1, INS, ABCC8

GO Terms for genes affiliated with Permanent Neonatal Diabetes Mellitus

Sources:
16Gene Ontology
See all sources

Cellular components related to Permanent Neonatal Diabetes Mellitus according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1voltage-gated potassium channel complexGO:0080768.9ABCC8, KCNJ11, KCNJ5

Biological processes related to Permanent Neonatal Diabetes Mellitus according to GeneCards/GeneDecks:

(show all 15)
idNameGO IDScoreTop Affiliating Genes
1negative regulation of gluconeogenesisGO:0457219.8GCK, INS
2positive regulation of glycolysisGO:0458219.8INS, GCK
3positive regulation of glycogen biosynthetic processGO:0457259.8GCK, INS
4detection of glucoseGO:0515949.5GCK, PDX1
5glucose transportGO:0157589.5INS, GCK
6potassium ion transportGO:0068139.5ABCC8, KCNJ5
7potassium ion transmembrane transportGO:0718059.5ABCC8, KCNJ11
8positive regulation of insulin secretionGO:0320249.4PDX1, GCK
9energy reserve metabolic processGO:0061129.2ABCC8, INS, KCNJ11
10endocrine pancreas developmentGO:0310189.1INS, PDX1, GCK
11glucose homeostasisGO:0425939.1INS, PDX1, GCK
12synaptic transmissionGO:0072688.9KCNJ5, KCNJ11, ABCC8
13regulation of insulin secretionGO:0507968.9ABCC8, INS, GCK, KCNJ11
14glucose metabolic processGO:0060068.8KCNJ11, PDX1, INS
15small molecule metabolic processGO:0442818.3ABCC8, INS, GCK, KCNJ11

Molecular functions related to Permanent Neonatal Diabetes Mellitus according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1ion channel bindingGO:0443259.4ABCC8, KCNJ11

Products for genes affiliated with Permanent Neonatal Diabetes Mellitus

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  • Proteins
  • Lysates
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Sources for Permanent Neonatal Diabetes Mellitus

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet