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Permanent neonatal diabetes mellitus 1(PDMI; PNDM1)

MedGen UID:
1717586
Concept ID:
C5393570
Disease or Syndrome
Synonym: GCK-Related Permanent Neonatal Diabetes Mellitus
 
Gene (location): GCK (7p13)
 
Monarch Initiative: MONDO:0100165
OMIM®: 606176

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 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include intrauterine growth restriction, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and results in dramatic catch-up growth. The course of PNDM varies by genotype. [from GeneReviews]
Authors:
Diva D De León  |  Charles A Stanley   view full author information

Additional description

From OMIM
Permanent neonatal diabetes mellitus-1 (PNDM1) is a rare autosomal recessive disorder characterized by severe hyperglycemia which requires insulin treatment soon after birth. The disorder results from a complete lack of glucokinase; total absence of basal insulin release was observed as well (Njolstad et al., 2001). PNDM is distinct from transient neonatal diabetes mellitus (TNDM; see 601410) and childhood-onset autoimmune diabetes mellitus type I (IDDM; 222100). Genetic Heterogeneity of Permanent Neonatal Diabetes Mellitus PNDM2 (618856) is caused by heterozygous mutation in the KCNJ11 (600937) gene on chromosome 11p15.1. PNDM3 (618857) is caused by heterozygous or homozygous mutation in the ABCC8 (600509) gene on chromosome 11p15.1. PNDM4 (618858) is caused by heterozygous or homozygous mutation in the INS (176730) gene on chromosome 11p15.5. Pancreatic agenesis, which results in exocrine pancreatic deficiency as well as permanent neonatal-onset diabetes mellitus, can be caused by mutation in the PDX1 gene (600733). Pancreatic agenesis associated with cerebellar agenesis (609069) can be caused by mutation in the PTF1A gene (607194). Pancreatic agenesis associated with congenital cardiac defects (600001) can be caused by mutation in the GATA6 gene (601656).  http://www.omim.org/entry/606176

Clinical features

From HPO
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Elevated hemoglobin A1c
MedGen UID:
892798
Concept ID:
C4073162
Finding
An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Diabetes mellitus type 1
MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Reduced C-peptide level
MedGen UID:
909412
Concept ID:
C4280764
Finding
A decreased concentration of C-peptide in the circulation. Since C-peptide is secreted in equimolar amounts to insulin, this feature correlates with reduced insulin secretion.

Professional guidelines

PubMed

Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E, Tarım Ö
J Clin Res Pediatr Endocrinol 2021 Feb 26;13(1):80-87. Epub 2020 Aug 21 doi: 10.4274/jcrpe.galenos.2020.2020.0093. PMID: 32820876Free PMC Article
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

Recent clinical studies

Etiology

Mouler M, Lebenthal Y, de Vries L, Yackobovitch-Gavan M, Averbuch NS, Fauret-Amsellem AL, Cavé H, Beltrand J, Polak M, Phillip M, Nimri R
Pediatr Diabetes 2022 Feb;23(1):45-54. Epub 2021 Dec 6 doi: 10.1111/pedi.13295. PMID: 34837310
Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
Kanakatti Shankar R, Pihoker C, Dolan LM, Standiford D, Badaru A, Dabelea D, Rodriguez B, Black MH, Imperatore G, Hattersley A, Ellard S, Gilliam LK; SEARCH for Diabetes in Youth Study Group
Pediatr Diabetes 2013 May;14(3):174-80. Epub 2012 Oct 10 doi: 10.1111/pedi.12003. PMID: 23050777Free PMC Article
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

Diagnosis

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
Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Redondo MJ, Hagopian WA, Oram R, Steck AK, Vehik K, Weedon M, Balasubramanyam A, Dabelea D
Diabetologia 2020 Oct;63(10):2040-2048. Epub 2020 Sep 7 doi: 10.1007/s00125-020-05211-7. PMID: 32894314Free PMC Article
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
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

Therapy

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
Garcin L, Kariyawasam D, Busiah K, Fauret-Amsellem AL, Le Bourgeois F, Vaivre-Douret L, Cavé H, Polak M, Beltrand J
Pediatr Diabetes 2018 Jun;19(4):663-669. Epub 2018 Mar 4 doi: 10.1111/pedi.12635. PMID: 29504184
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
Hashimoto Y, Dateki S, Hirose M, Satomura K, Sawada H, Mizuno H, Sugihara S, Maruyama K, Urakami T, Sugawara H, Shirai K, Yorifuji T
Pediatr Diabetes 2017 Nov;18(7):532-539. Epub 2016 Sep 29 doi: 10.1111/pedi.12447. PMID: 27681997
Polak M, Shield J
Semin Neonatol 2004 Feb;9(1):59-65. doi: 10.1016/S1084-2756(03)00064-2. PMID: 15013476

Prognosis

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
Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E, Tarım Ö
J Clin Res Pediatr Endocrinol 2021 Feb 26;13(1):80-87. Epub 2020 Aug 21 doi: 10.4274/jcrpe.galenos.2020.2020.0093. PMID: 32820876Free PMC Article
Redondo MJ, Hagopian WA, Oram R, Steck AK, Vehik K, Weedon M, Balasubramanyam A, Dabelea D
Diabetologia 2020 Oct;63(10):2040-2048. Epub 2020 Sep 7 doi: 10.1007/s00125-020-05211-7. PMID: 32894314Free PMC Article
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
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

Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E, Tarım Ö
J Clin Res Pediatr Endocrinol 2021 Feb 26;13(1):80-87. Epub 2020 Aug 21 doi: 10.4274/jcrpe.galenos.2020.2020.0093. PMID: 32820876Free PMC Article
Redondo MJ, Hagopian WA, Oram R, Steck AK, Vehik K, Weedon M, Balasubramanyam A, Dabelea D
Diabetologia 2020 Oct;63(10):2040-2048. Epub 2020 Sep 7 doi: 10.1007/s00125-020-05211-7. PMID: 32894314Free PMC Article
Johnson MB, De Franco E, Greeley SAW, Letourneau LR, Gillespie KM; International DS-PNDM Consortium, Wakeling MN, Ellard S, Flanagan SE, Patel KA, Hattersley AT
Diabetes 2019 Jul;68(7):1528-1535. Epub 2019 Apr 8 doi: 10.2337/db19-0045. PMID: 30962220Free PMC Article
Riahi Y, Israeli T, Cerasi E, Leibowitz G
Diabetes Obes Metab 2018 Sep;20 Suppl 2:95-103. doi: 10.1111/dom.13379. PMID: 30230182
Hashimoto Y, Dateki S, Hirose M, Satomura K, Sawada H, Mizuno H, Sugihara S, Maruyama K, Urakami T, Sugawara H, Shirai K, Yorifuji T
Pediatr Diabetes 2017 Nov;18(7):532-539. Epub 2016 Sep 29 doi: 10.1111/pedi.12447. PMID: 27681997

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