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Permanent neonatal diabetes mellitus(PNDM)

MedGen UID:
371484
•Concept ID:
C1833104
•
Disease or Syndrome
Synonyms: ABCC8-Related Permanent Neonatal Diabetes Mellitus; INS-Related Permanent Neonatal Diabetes Mellitus; KCNJ11-Related Permanent Neonatal Diabetes Mellitus; PDX1-Related Permanent Neonatal Diabetes Mellitus; Permanent diabetes mellitus of infancy; PNDM
SNOMED CT: Permanent diabetes mellitus of infancy (609565001); Permanent neonatal diabetes mellitus (609565001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (Orphanet)
Autosomal dominant inheritance (Orphanet)
 
Genes (locations): ABCC8 (11p15.1); GCK (7p13); INS (11p15.5); KCNJ11 (11p15.1); PDX1 (13q12.2)
 
Monarch Initiative: MONDO:0100164
OMIM® Phenotypic series: PS606176
Orphanet: ORPHA99885

Disease characteristics

Excerpted from the GeneReview: Permanent Neonatal Diabetes Mellitus
Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to age 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and history of intrauterine growth deficiency. Therapy with insulin and/or oral hypoglycemic medications (in some molecular causes of PNDM) can correct the hyperglycemia and result in dramatic catch-up growth. The course of PNDM varies by genotype. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Diva D De León  |  Sara E Pinney   view full author information

Additional description

From MedlinePlus Genetics
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.

A small number of individuals with permanent neonatal diabetes mellitus have an underdeveloped pancreas. Because the pancreas produces digestive enzymes as well as secreting insulin and other hormones, affected individuals experience digestive problems such as fatty stools and an inability to absorb fat-soluble vitamins.

Individuals with permanent neonatal diabetes mellitus experience slow growth before birth (intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration) and are unable to gain weight and grow at the expected rate (failure to thrive).

In some cases, people with permanent neonatal diabetes mellitus also have certain neurological problems, including developmental delay and recurrent seizures (epilepsy). This combination of developmental delay, epilepsy, and neonatal diabetes is called DEND syndrome. Intermediate DEND syndrome is a similar combination but with milder developmental delay and without epilepsy.  https://medlineplus.gov/genetics/condition/permanent-neonatal-diabetes-mellitus

Professional guidelines

PubMed

Recent clinical advances of glucokinase activators in the treatment of diabetes mellitus type 2.
Li W, Zhang X, Sun Y, Liu Z
Pharmazie 2020 Jun 1;75(6):230-235. doi: 10.1691/ph.2020.0409. PMID: 32539915
Permanent neonatal diabetes mellitus--the importance of diabetes differential diagnosis in neonates and infants.
Rubio-Cabezas O, Klupa T, Malecki MT; CEED3 Consortium
Eur J Clin Invest 2011 Mar;41(3):323-33. Epub 2010 Nov 4 doi: 10.1111/j.1365-2362.2010.02409.x. PMID: 21054355
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.
Tonini G, Bizzarri C, Bonfanti R, Vanelli M, Cerutti F, Faleschini E, Meschi F, Prisco F, Ciacco E, Cappa M, Torelli C, Cauvin V, Tumini S, Iafusco D, Barbetti F; Early-Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology
Diabetologia 2006 Sep;49(9):2210-3. Epub 2006 Jul 1 doi: 10.1007/s00125-006-0329-x. PMID: 16816952

Recent clinical studies

Etiology

Very low birth weight newborn with diabetes mellitus due to pancreas agenesis managed with insulin pump reservoir filled with undiluted insulin: 16-month follow-up.
Zanfardino A, Piscopo A, Curto S, Schiaffini R, Rollato AS, Testa V, Miraglia Del Giudice E, Barbetti F, Iafusco D
Diabetes Metab Syndr 2022 Jul;16(7):102561. Epub 2022 Jun 30 doi: 10.1016/j.dsx.2022.102561. PMID: 35809554
Long-term follow-up of a child with Wolcott-Rallison syndrome.
Shah N, Karguppikar MB, Khadilkar V, Khadilkar A
BMJ Case Rep 2021 May 13;14(5) doi: 10.1136/bcr-2021-242376. PMID: 33986015Free PMC Article
Monogenic Forms of Diabetes Mellitus.
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
ADHD, learning difficulties and sleep disturbances associated with KCNJ11-related neonatal diabetes.
Landmeier KA, Lanning M, Carmody D, Greeley SAW, Msall ME
Pediatr Diabetes 2017 Nov;18(7):518-523. Epub 2016 Aug 24 doi: 10.1111/pedi.12428. PMID: 27555491Free PMC Article
Mother and daughter carrying the same KCNJ11 mutation but with a different response to switching from insulin to sulfonylurea.
Russo C, Salina A, Aloi C, Iafusco D, Lorini R, d'Annunzio G
Diabetes Res Clin Pract 2011 Nov;94(2):e50-2. Epub 2011 Aug 25 doi: 10.1016/j.diabres.2011.07.039. PMID: 21871684

Diagnosis

Genetic and clinical heterogeneity of permanent neonatal diabetes mellitus: a single tertiary centre experience.
Laimon W, El-Ziny M, El-Hawary A, Elsharkawy A, Salem NA, Aboelenin HM, Awad MH, Flanagan SE, De Franco E
Acta Diabetol 2021 Dec;58(12):1689-1700. Epub 2021 Aug 23 doi: 10.1007/s00592-021-01788-6. PMID: 34426871
Long-term follow-up of a child with Wolcott-Rallison syndrome.
Shah N, Karguppikar MB, Khadilkar V, Khadilkar A
BMJ Case Rep 2021 May 13;14(5) doi: 10.1136/bcr-2021-242376. PMID: 33986015Free PMC Article
Genetic Factors of Diabetes.
Antosik K, Borowiec M
Arch Immunol Ther Exp (Warsz) 2016 Dec;64(Suppl 1):157-160. Epub 2017 Jan 12 doi: 10.1007/s00005-016-0432-8. PMID: 28083605
Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.
Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL
Hum Mutat 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. PMID: 19790256
Neonatal diabetes.
Tammaro P
Endocr Dev 2007;11:70-82. doi: 10.1159/000111059. PMID: 17986828

Therapy

Meglitinide (repaglinide) therapy in permanent neonatal diabetes mellitus: two case reports.
Razzaghy-Azar M, Nourbakhsh M, Talea A, Mohammad Amoli M, Nourbakhsh M, Larijani B
J Med Case Rep 2021 Oct 25;15(1):535. doi: 10.1186/s13256-021-03052-5. PMID: 34696808Free PMC Article
Insulin therapy in neonatal diabetes mellitus: a review of the literature.
Rabbone I, Barbetti F, Gentilella R, Mossetto G, Bonfanti R, Maffeis C, Iafusco D, Piccinno E
Diabetes Res Clin Pract 2017 Jul;129:126-135. Epub 2017 Apr 13 doi: 10.1016/j.diabres.2017.04.007. PMID: 28527303
Mother and daughter carrying the same KCNJ11 mutation but with a different response to switching from insulin to sulfonylurea.
Russo C, Salina A, Aloi C, Iafusco D, Lorini R, d'Annunzio G
Diabetes Res Clin Pract 2011 Nov;94(2):e50-2. Epub 2011 Aug 25 doi: 10.1016/j.diabres.2011.07.039. PMID: 21871684
Transfer from insulin to sulfonylurea treatment in a chinese patient with permanent neonatal diabetes mellitus due to a KCNJ11 R201H mutation.
Xiao X, Wang T, Li W, Song H, Gong C, Diao C, Yu M, Yuan T, Zhang Y, Sun X, Zhang Q, Lu K, Wang H, Schmitz O, Hansen T
Horm Metab Res 2009 Jul;41(7):580-2. Epub 2009 Feb 26 doi: 10.1055/s-0029-1192020. PMID: 19247925
Neonatal and very-early-onset diabetes mellitus.
Polak M, Shield J
Semin Neonatol 2004 Feb;9(1):59-65. doi: 10.1016/S1084-2756(03)00064-2. PMID: 15013476

Prognosis

Genetic and clinical heterogeneity of permanent neonatal diabetes mellitus: a single tertiary centre experience.
Laimon W, El-Ziny M, El-Hawary A, Elsharkawy A, Salem NA, Aboelenin HM, Awad MH, Flanagan SE, De Franco E
Acta Diabetol 2021 Dec;58(12):1689-1700. Epub 2021 Aug 23 doi: 10.1007/s00592-021-01788-6. PMID: 34426871
Monogenic Forms of Diabetes Mellitus.
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
Epidemiology, clinical characteristics, and genetic etiology of neonatal diabetes in Japan.
Nagashima K, Tanaka D, Inagaki N
Pediatr Int 2017 Feb;59(2):129-133. doi: 10.1111/ped.13199. PMID: 27809389
Permanent neonatal diabetes mellitus in Jordan.
Abujbara MA, Liswi MI, El-Khateeb MS, Flanagan SE, Ellard S, Ajlouni KM
J Pediatr Endocrinol Metab 2014 Sep;27(9-10):879-83. doi: 10.1515/jpem-2014-0069. PMID: 24825091
Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.
Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL
Hum Mutat 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. PMID: 19790256

Clinical prediction guides

Very low birth weight newborn with diabetes mellitus due to pancreas agenesis managed with insulin pump reservoir filled with undiluted insulin: 16-month follow-up.
Zanfardino A, Piscopo A, Curto S, Schiaffini R, Rollato AS, Testa V, Miraglia Del Giudice E, Barbetti F, Iafusco D
Diabetes Metab Syndr 2022 Jul;16(7):102561. Epub 2022 Jun 30 doi: 10.1016/j.dsx.2022.102561. PMID: 35809554
A novel mutation of KCNJ11 gene in a patient with permanent neonatal diabetes mellitus.
Chang WL, Huang CJ, Lei TH, Niu DM, Chiu CY, Jap TS
Diabetes Res Clin Pract 2014 Apr;104(1):e29-32. Epub 2014 Jan 8 doi: 10.1016/j.diabres.2013.12.058. PMID: 24468099
Focus on Kir6.2: a key component of the ATP-sensitive potassium channel.
Haider S, Antcliff JF, Proks P, Sansom MS, Ashcroft FM
J Mol Cell Cardiol 2005 Jun;38(6):927-36. doi: 10.1016/j.yjmcc.2005.01.007. PMID: 15910877
Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2.
Zung A, Glaser B, Nimri R, Zadik Z
J Clin Endocrinol Metab 2004 Nov;89(11):5504-7. doi: 10.1210/jc.2004-1241. PMID: 15531505
Permanent neonatal diabetes mellitus: clinical presentation and epidemiology in Oman.
Bappal B, Raghupathy P, de Silva V, Khusaiby SM
Arch Dis Child Fetal Neonatal Ed 1999 May;80(3):F209-12. doi: 10.1136/fn.80.3.f209. PMID: 10212083Free PMC Article

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