Permanent Neonatal Diabetes Mellitus malady

NIH Rare Diseases: 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).³⁰

MalaCards: Permanent Neonatal Diabetes Mellitus, also known as permanent diabetes mellitus of infancy, is related to type 1 diabetes mellitus and type 2 diabetes mellitus. An important gene associated with Permanent Neonatal Diabetes Mellitus is KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11), and among its related pathways are Potassium transporters- inward current and Selected targets of HNF1. The drug chromium picolinate and the compounds levosimendan and chromium picolinate have been mentioned in the context of this disorder. Affiliated tissues include pancreas, and related mouse phenotypes are homeostasis/metabolism and endocrine/exocrine gland.

Genetics Home Reference: 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.¹⁷

Wikipedia: A newly identified and potentially treatable form of monogenic diabetes is the neonatal diabetes caused...⁴⁴ more...

OMIM: 606176

GeneReviews summary for dmn

permanent neonatal diabetes mellitus 15 30 16 17 permanent diabetes mellitus of infancy 15 30 16 diabetes mellitus, permanent neonatal 33 43

pndm 30 17 diabetes mellitus 43

Diseases related to permanent neonatal diabetes mellitus by text searches and GeneDecks gene sharing:

(show top 50)    (show all 380)

id	Related Disease	Score	Top Affiliating Genes
1	type 1 diabetes mellitus	38.7	GCK, INS, PDX1
2	type 2 diabetes mellitus	38.5	ABCC8, PDX1, INS, KCNJ5, KCNJ11, GCK
3	gestational diabetes	36.0	ABCC8, INS, KCNJ11, GCK
4	insulin resistance	35.3	ABCC8, PDX1, INS, KCNJ11, GCK
5	hypertension	35.3	GCK, KCNJ11, KCNJ5, INS
6	obesity	34.2	ABCC8, PDX1, INS, KCNJ5, KCNJ11, GCK
7	coronary heart disease	33.6	INS, KCNJ5, KCNJ11
8	transient neonatal diabetes mellitus	33.1	ABCC8, INS, KCNJ11
9	pancreatitis	32.6	ABCC8, PDX1, INS, KCNJ5, KCNJ11, GCK
10	neonatal diabetes mellitus	32.4	GCK, KCNJ11, KCNJ5, INS, PDX1, ABCC8
11	diabetes mellitus	32.2	ABCC8, PDX1, INS, KCNJ5, KCNJ11, GCK
12	myocardial infarction	32.0	PDX1, INS, KCNJ5, KCNJ11
13	hyperglycemia	31.9	ABCC8, PDX1, INS, KCNJ11, GCK
14	hypoglycemia	30.7	ABCC8, PDX1, INS, KCNJ5, KCNJ11, GCK
15	essential hypertension	30.6	INS, KCNJ5, KCNJ11, GCK
16	maturity-onset diabetes of the young	30.4	PDX1, INS, KCNJ11, GCK
17	diabetes, type 2	30.3	ABCC8, INS, KCNJ11
18	glucose intolerance	30.2	GCK, KCNJ11, INS, ABCC8
19	diabetes mellitus, noninsulin-dependent	29.9	GCK, ABCC8
20	acute myocardial infarction	29.8	KCNJ11, KCNJ5, INS
21	twinning	29.5	ABCC8, INS, GCK
22	ischemia	29.0	ABCC8, INS, KCNJ5, KCNJ11, GCK
23	arterial calcification	28.8	KCNJ11, INS
24	cerebritis	28.8	ABCC8, PDX1, INS, KCNJ5, GCK
25	pancreatic agenesis	28.1	ABCC8, GCK, KCNJ11, INS, PDX1
26	duodenitis	27.8	PDX1, INS, GCK
27	glucagonoma	27.7	INS, PDX1
28	hyperinsulinemic hypoglycemia	27.7	INS, ABCC8
29	hyperinsulinism	27.4	ABCC8, INS, KCNJ5, KCNJ11, GCK
30	insulinoma	26.6	ABCC8, PDX1, INS, KCNJ5, KCNJ11, GCK
31	adenoma	25.6	ABCC8, INS, KCNJ5, GCK
32	hyperinsulinism-hyperammonemia syndrome	12.9	KCNJ5, INS
33	hyperinsulinism, focal	12.9	KCNJ11, ABCC8
34	hyperaldosteronism	12.8	KCNJ5, INS
35	adrenal adenoma	12.8	KCNJ5, INS
36	ketoacidosis due to scot deficiency	12.7	INS, ABCC8
37	gastrinoma	12.7	INS, PDX1
38	hypokalemia	12.7	INS, KCNJ5
39	recessive developmental delay, small stature, microcephaly and brain calcifications	12.6	KCNJ11, ABCC8
40	3-hydroxyacyl-coa dehydrogenase deficiency	12.5	GCK, INS
41	diabetes, permanent neonatal	12.4	ABCC8, KCNJ5, KCNJ11
42	epilepsy syndrome	12.3	KCNJ11, KCNJ5, ABCC8
43	beckwith-wiedemann syndrome	12.3	KCNJ11, INS, ABCC8
44	arrhythmogenic right ventricular dysplasia/cardiomyopathy multi-gene panels	12.2	KCNJ5, INS, ABCC8
45	nephropathy	12.2
46	bartter disease	12.1	KCNJ11, KCNJ5, ABCC8
47	leucine-sensitive hypoglycemia of infancy	12.1	GCK, KCNJ11, ABCC8
48	persistent hyperinsulinemic hypoglycemia of infancy	12.1	ABCC8, KCNJ11, GCK
49	hyperammonemia with hypoornithinemia	12.0	GCK, KCNJ11, ABCC8
50	acute insulin response	11.9	KCNJ11, KCNJ5, INS, ABCC8

Clinical features from OMIM: 606176

Approved drugs:

Drug clinical trials:

Inferred drug relations via UMLS/NDF-RT:

^43 28 chromium picolinate

MalaCards organs/tissues related to permanent neonatal diabetes mellitus:

²²

MGI Mouse Phenotypes related to permanent neonatal diabetes mellitus:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	homeostasis/metabolism phenotype	MP:0005376	7.6	ABCC8, PDX1, INS, KCNJ11, GCK
2	endocrine/exocrine gland phenotype	MP:0005379	7.3	ABCC8, PDX1, INS, KCNJ11, GCK

Articles related to permanent neonatal diabetes mellitus:

(show all 12)

id	Title	Authors	Year	Affiliating Genes
1	KCNJ11 activating mutations cause both transient and permanent neonatal diabetes mellitus in Cypriot patients. (21352428)	Ioannou Y.S.... Skordis N.	2011	KCNJ11
2	A new variant of a known mutation in two siblings wit h permanent neonatal diabetes mellitus. (21823539)	Aycan Z.... Ceylaner S.	2011	INS
3	Transfer from insulin to sulfonylurea treatment in a chinese patient with permanent neonatal diabetes mellitus due to a KCNJ11 R201H mutation. (19247925)	Xiao X.... Hansen T.	2009	INS
4	Improved diabetic control during oral sulfonylurea tr eatment in two children with permanent neonatal diabetes mellitus. (19774848)	Ting W.H.... Lee Y.J.	2009	KCNJ11
5	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)	Della Manna T.... Reis A.F.	2008	KCNJ11
6	Permanent neonatal diabetes mellitus caused by a novel homozygous (T168A) glucokinase (GCK) mutation: initial response to oral sulphonylurea therapy. (18571549)	Turkkahraman D.... Gloyn A.L.	2008	GCK
7	Permanent neonatal diabetes mellitus due to a C96Y heterozygous mutation in the insulin gene. A case report. (18981553)	Ahamed A.... Edghill E.L.	2008	INS
8	A mutation in the TMD0-L0 region of sulfonylurea receptor-1 (L225P) causes permanent neonatal diabetes mellitus (PNDM). (17317760)	Masia R.... Nichols C.G.	2007	ABCC8
9	Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2. (17491708)	Skupien J.... Sieradzki J.	2006	KCNJ11, INS, KCNJ5
10	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)	Tonini G.... Barbetti F.	2006	KCNJ11, INS
11	Permanent neonatal diabetes mellitus manifesting as diabetic ketoacidosis. (14976569)	Lee J.H.... Hsieh W.S.	2003	INS
12	Permanent neonatal diabetes mellitus: clinical presentation and epidemiology in Oman. (10212083)	Bappal B.... Khusaiby S.M.	1999	INS

Genes related to permanent neonatal diabetes mellitus according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	KCNJ11	potassium inwardly-rectifying channel, subfamily J, member 11	11.1	Publications, Summaries
2	KCNJ5	potassium inwardly-rectifying channel, subfamily J, member 5	11.0	Publications
3	PDX1	pancreatic and duodenal homeobox 1	11.0
4	GCK	glucokinase (hexokinase 4)	11.0	Publications
5	ABCC8	ATP-binding cassette, sub-family C (CFTR/MRP), member 8	11.0	Publications
6	INS	insulin	11.0	Publications

Pathways related to permanent neonatal diabetes mellitus according to GeneDecks:

(show all 11)

id	Pathway	Score	Top Affiliating Genes
1	Potassium transporters- inward current10	9.5	KCNJ5, KCNJ11
2	Selected targets of HNF110	9.5	INS, PDX1
3	Inwardly rectifying K+ channels38	9.4	ABCC8, KCNJ11
4	MODY (Maturity-Onset Diabetes of Young)36	9.3	INS, GCK
5	Development Leptin signaling via PI3K-dependent pathway10	9.2	ABCC8, KCNJ11
6	Maturity onset diabetes of the young20	9.0	INS, PDX1, GCK
7	Potassium transporters- outward current10	9.0	KCNJ5, ABCC8, KCNJ11
8	Development_Leptin signaling via PI3K-dependent pathway41	8.9	ABCC8, KCNJ11
9	Antiarrhythmic Pathway, Pharmacodynamics34	8.9	ABCC8, KCNJ5, KCNJ11
10	Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics34	7.8	GCK, KCNJ11, INS, PDX1, ABCC8
11	Type II diabetes mellitus20	7.8	INS, ABCC8, PDX1, KCNJ11, GCK

Compounds related to permanent neonatal diabetes mellitus according to GeneDecks:

(show all 50)

id	Compound	Score	Top Affiliating Genes
1	levosimendan32 9 9	12.0	KCNJ5, KCNJ11
2	chromium picolinate32	9.7	GCK, INS
3	cibenzoline32	9.6	ABCC8, KCNJ11
4	proglucagon32	9.6	PDX1, GCK
5	nicotinamide32 9 9	11.6	PDX1, INS
6	benzopyran32	9.6	ABCC8, KCNJ5
7	dicyandiamide32	9.6	KCNJ5, ABCC8
8	nicorandil32	9.6	KCNJ5, ABCC8
9	pinacidil32	9.5	ABCC8, KCNJ5
10	cromakalim32	9.5	ABCC8, KCNJ5
11	aicar32 42 9 18 9	13.5	GCK, INS
12	phentolamine32 9 9	11.5	ABCC8, KCNJ5
13	minoxidil32 9 9	11.5	KCNJ5, ABCC8
14	meglitinide32	9.5	ABCC8, INS
15	mitiglinide32 9 9	11.5	INS, ABCC8
16	chlorpropamide32 9 9	11.5	INS, ABCC8
17	2-deoxyglucose32	9.2	GCK, INS
18	preproinsulin32	9.2	PDX1, INS, GCK
19	i-app32	9.2	GCK, INS, PDX1
20	incretin32	9.2	PDX1, INS, GCK
21	mgadp32	9.2	KCNJ11, KCNJ5, ABCC8
22	streptozotocin32	9.2	PDX1, INS, GCK
23	Glyburide9 9	10.2	KCNJ11, KCNJ5, ABCC8
24	gliclazide32 34 9 9	12.1	ABCC8, INS, KCNJ11
25	glipizide32 9 9	11.1	KCNJ5, INS, ABCC8
26	pip232	8.9	KCNJ11, ABCC8
27	lactate32	8.9	INS, GCK, KCNJ5
28	lysine32	8.9	KCNJ5, KCNJ11, ABCC8
29	c-peptide32	8.8	KCNJ11, GCK, INS, PDX1
30	glycogen32 18	9.7	GCK, INS, ABCC8
31	repaglinide32 42 9 9	11.7	INS, KCNJ11, KCNJ5, ABCC8
32	glimepiride32 34 9 9	11.7	KCNJ5, KCNJ11, ABCC8, INS
33	nateglinide32 42 9 9	11.7	KCNJ11, KCNJ5, ABCC8, INS
34	glibenclamide32 34	9.7	KCNJ5, INS, ABCC8, KCNJ11
35	leucine32	8.6	ABCC8, KCNJ11, GCK
36	fatty acid32	8.6	ABCC8, INS, GCK
37	metformin32 34 9 9	11.5	KCNJ11, ABCC8, INS, GCK
38	potassium32 9 18 9	11.5	KCNJ5, ABCC8, KCNJ11, GCK
39	magnesium32 9 18 9	11.5	GCK, KCNJ11, KCNJ5, ABCC8
40	adp32 18	9.4	KCNJ5, GCK, KCNJ11, ABCC8
41	atp32	8.4	GCK, ABCC8, KCNJ5, KCNJ11
42	arginine32	8.4	KCNJ11, INS, ABCC8, GCK
43	lipid32	8.2	INS, ABCC8, GCK, KCNJ5
44	diazoxide32 42 9 9	11.1	ABCC8, INS, KCNJ5, KCNJ11, GCK
45	tolbutamide32 34 9 9	11.1	ABCC8, INS, KCNJ5, KCNJ11, GCK
46	glutamate32	8.0	KCNJ11, KCNJ5, INS, ABCC8, GCK
47	calcium32 9 18 9	10.9	KCNJ11, KCNJ5, PDX1, GCK, ABCC8
48	katp32	7.6	KCNJ11, KCNJ5, INS, PDX1, ABCC8, GCK
49	sulfonylurea32	7.6	KCNJ5, INS, PDX1, ABCC8, KCNJ11, GCK
50	glucose32	7.5	INS, KCNJ5, KCNJ11, GCK, PDX1, ABCC8

Cellular components related to permanent neonatal diabetes mellitus according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	secretory granule	GO:030141	9.3	GCK, INS
2	T-tubule	GO:030315	9.3	KCNJ11, KCNJ5
3	voltage-gated potassium channel complex	GO:008076	8.7	KCNJ11, KCNJ5, ABCC8

Biological processes related to permanent neonatal diabetes mellitus according to GeneDecks:

(show all 14)

id	Name	GO ID	Score	Top Affiliating Genes
1	detection of glucose	GO:051594	9.6	GCK, PDX1
2	negative regulation of gluconeogenesis	GO:045721	9.6	GCK, INS
3	potassium ion transmembrane transport	GO:071805	9.4	ABCC8, KCNJ11
4	positive regulation of glycolysis	GO:045821	9.4	INS, GCK
5	positive regulation of glycogen biosynthetic process	GO:045725	9.4	INS, GCK
6	glucose transport	GO:015758	9.2	GCK, INS
7	glucose metabolic process	GO:006006	9.2	KCNJ11, INS, PDX1
8	potassium ion transport	GO:006813	9.2	KCNJ5, ABCC8
9	endocrine pancreas development	GO:031018	9.1	GCK, PDX1, INS
10	glucose homeostasis	GO:042593	9.0	GCK, INS, PDX1
11	energy reserve metabolic process	GO:006112	8.9	KCNJ11, INS, ABCC8
12	synaptic transmission	GO:007268	8.8	KCNJ11, KCNJ5, ABCC8
13	regulation of insulin secretion	GO:050796	8.4	INS, GCK, KCNJ11, ABCC8
14	small molecule metabolic process	GO:044281	7.8	KCNJ11, GCK, ABCC8, INS

Molecular functions related to permanent neonatal diabetes mellitus according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	ion channel binding	GO:044325	9.2	KCNJ11, ABCC8