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Transient neonatal diabetes mellitus 1

MedGen UID:
371317
Concept ID:
C1832386
Disease or Syndrome
Synonyms: Chromosome 6-associated transient diabetes mellitus; Diabetes mellitus, 6q24-related transient neonatal; Diabetes Mellitus, 6q24-Related Transient Neonatal; Diabetes mellitus, transient neonatal
SNOMED CT: Diabetes mellitus, transient neonatal 1 (609579009); TNDM1 (609579009)
 
Genes (locations): HYMAI (6q24.2); PLAGL1 (6q24.2); ZFP57 (6p22.1)
OMIM®: 601410

Disease characteristics

6q24-related transient neonatal diabetes mellitus (6q24-TNDM) is defined as transient neonatal diabetes mellitus caused by genetic aberrations of the imprinted locus at 6q24. The cardinal features are: severe intrauterine growth retardation, hyperglycemia that begins in the neonatal period in a term infant and resolves by age 18 months, dehydration, and absence of ketoacidosis. Macroglossia and umbilical hernia are often present. In the subset of children with ZFP57 pathogenic variants, other manifestations can include structural brain abnormalities, developmental delay, and congenital heart disease. Diabetes mellitus usually starts within the first week of life and lasts on average three months but can last longer than a year. Although insulin is usually required initially, the need for insulin gradually declines over time. Intermittent episodes of hyperglycemia may occur in childhood, particularly during intercurrent illnesses. Diabetes mellitus may recur in adolescence or later in adulthood. Women who have had 6q24-TNDM are at risk for relapse during pregnancy.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Isabel Karen Temple  |  Deborah JG Mackay  |  Louise Esther Docherty   view full author information

Additional descriptions

From OMIM
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. Genetic Heterogeneity of Transient Neonatal Diabetes TNDM2 (610374) is caused by mutation in the ABCC8 gene (600509) on chromosome 11p15.1. TNDM3 (610582) is caused by mutation in the KCNJ11 gene (600937), also located on 11p15.1.  http://www.omim.org/entry/601410
From GHR
6q24-related transient neonatal diabetes mellitus is a type of diabetes that occurs in infants. 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. People with 6q24-related transient neonatal diabetes mellitus experience very slow growth before birth (severe intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration), usually beginning in the first week of life. Signs and symptoms of this form of diabetes are transient, which means that they gradually lessen over time and generally disappear between the ages of 3 months and 18 months. Diabetes may recur, however, especially during childhood illnesses or pregnancy. Up to half of individuals with 6q24-related transient neonatal diabetes mellitus develop permanent diabetes mellitus later in life. Other features of 6q24-related transient neonatal diabetes mellitus that occur in some affected individuals include an unusually large tongue (macroglossia); a soft out-pouching around the belly-button (an umbilical hernia); malformations of the brain, heart, or kidneys; weak muscle tone (hypotonia); deafness; and developmental delay.  http://ghr.nlm.nih.gov/condition/6q24-related-transient-neonatal-diabetes-mellitus

Clinical features

Intrauterine growth retardation
MedGen UID:
342890
Concept ID:
C1853481
Finding
Severe failure to thrive
MedGen UID:
343373
Concept ID:
C1855514
Finding
Transient neonatal diabetes mellitus
MedGen UID:
446909
Concept ID:
CN007256
Finding
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
Hyperglycemia means high blood sugar or glucose. Glucose comes from the foods you eat. Insulin is a hormone that moves glucose into your cells to give them energy. Hyperglycemia happens when your body doesn't make enough insulin or can't use it the right way. People with diabetes can get hyperglycemia from not eating the right foods or not taking medicines correctly. Other problems that can raise blood sugar include infections, certain medicines, hormone imbalances, or severe illnesses.
Dehydration
MedGen UID:
776589
Concept ID:
C2712335
Finding
Transient neonatal diabetes mellitus
MedGen UID:
446909
Concept ID:
CN007256
Finding

Professional guidelines

PubMed

Shaffer LG, Agan N, Goldberg JD, Ledbetter DH, Longshore JW, Cassidy SB
Genet Med 2001 May-Jun;3(3):206-11. doi: 10.109700125817-200105000-00011. PMID: 11388763Free PMC Article

Suggested Reading

PubMed

Gardner RJ, Mackay DJ, Mungall AJ, Polychronakos C, Siebert R, Shield JP, Temple IK, Robinson DO
Hum Mol Genet 2000 Mar 1;9(4):589-96. PMID: 10699182

Recent clinical studies

Etiology

Fung GP, Chan LM, Ho YC, To WK, Chan HB, Lao TT
Early Hum Dev 2014 Sep;90(9):527-30. Epub 2014 May 10 doi: 10.1016/j.earlhumdev.2014.04.006. [Epub ahead of print] PMID: 24819408
Boonen SE, Mackay DJ, Hahnemann JM, Docherty L, Grønskov K, Lehmann A, Larsen LG, Haemers AP, Kockaerts Y, Dooms L, Vu DC, Ngoc CT, Nguyen PB, Kordonouri O, Sundberg F, Dayanikli P, Puthi V, Acerini C, Massoud AF, Tümer Z, Temple IK
Diabetes Care 2013 Mar;36(3):505-12. Epub 2012 Nov 12 doi: 10.2337/dc12-0700. [Epub ahead of print] PMID: 23150280Free PMC Article
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. [Epub ahead of print] PMID: 23050777Free PMC Article
Iafusco D, Massa O, Pasquino B, Colombo C, Iughetti L, Bizzarri C, Mammì C, Lo Presti D, Suprani T, Schiaffini R, Nichols CG, Russo L, Grasso V, Meschi F, Bonfanti R, Brescianini S, Barbetti F; Early Diabetes Study Group of ISPED
Acta Diabetol 2012 Oct;49(5):405-8. Epub 2011 Sep 28 doi: 10.1007/s00592-011-0331-8. [Epub ahead of print] PMID: 21953423Free PMC Article
Klupa T, Kozek E, Nowak N, Cyganek K, Gach A, Milewicz T, Czajkowski K, Tolloczko J, Mlynarski W, Malecki MT
J Clin Endocrinol Metab 2010 Aug;95(8):3599-604. Epub 2010 May 13 doi: 10.1210/jc.2010-0096. [Epub ahead of print] PMID: 20466780

Diagnosis

Demirbilek H, Arya VB, Ozbek MN, Houghton JA, Baran RT, Akar M, Tekes S, Tuzun H, Mackay DJ, Flanagan SE, Hattersley AT, Ellard S, Hussain K
Eur J Endocrinol 2015 Jun;172(6):697-705. Epub 2015 Mar 9 doi: 10.1530/EJE-14-0852. [Epub ahead of print] PMID: 25755231Free PMC Article
Mackay D, Bens S, Perez de Nanclares G, Siebert R, Temple IK
Eur J Hum Genet 2014 Sep;22(9) Epub 2014 Feb 26 doi: 10.1038/ejhg.2014.27. [Epub ahead of print] PMID: 24569603Free PMC Article
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. [Epub ahead of print] PMID: 23050777Free PMC Article
Mihai B, Mihai C, Cijevschi-Prelipcean C, Lăcătuşu C
Rev Med Chir Soc Med Nat Iasi 2012 Jul-Sep;116(3):700-7. PMID: 23272513
Hewes HA, Dudley NC, Adelgais KM
Pediatr Emerg Care 2010 Dec;26(12):930-1. doi: 10.1097/PEC.0b013e3181fe91a4. PMID: 21131807

Therapy

Passanisi S, Timpanaro T, Lo Presti D, Mammì C, Caruso-Nicoletti M
Diabetes Technol Ther 2014 Dec;16(12):880-4. doi: 10.1089/dia.2014.0055. PMID: 25437016Free PMC Article
Catli G, Abaci A, Flanagan SE, Anik A, Ellard S, Bober E
Diabetes Res Clin Pract 2013 Jan;99(1):e5-8. Epub 2012 Oct 27 doi: 10.1016/j.diabres.2012.10.009. [Epub ahead of print] PMID: 23107109
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. [Epub ahead of print] PMID: 23050777Free PMC Article
Oztekin O, Durmaz E, Kalay S, Flanagan SE, Ellard S, Bircan I
J Perinatol 2012 Aug;32(8):645-7. doi: 10.1038/jp.2012.46. PMID: 22842804
Hewes HA, Dudley NC, Adelgais KM
Pediatr Emerg Care 2010 Dec;26(12):930-1. doi: 10.1097/PEC.0b013e3181fe91a4. PMID: 21131807

Prognosis

Demirbilek H, Arya VB, Ozbek MN, Houghton JA, Baran RT, Akar M, Tekes S, Tuzun H, Mackay DJ, Flanagan SE, Hattersley AT, Ellard S, Hussain K
Eur J Endocrinol 2015 Jun;172(6):697-705. Epub 2015 Mar 9 doi: 10.1530/EJE-14-0852. [Epub ahead of print] PMID: 25755231Free PMC Article
Alkorta-Aranburu G, Carmody D, Cheng YW, Nelakuditi V, Ma L, Dickens JT, Das S, Greeley SA, del Gaudio D
Mol Genet Metab 2014 Dec;113(4):315-20. Epub 2014 Sep 28 doi: 10.1016/j.ymgme.2014.09.007. [Epub ahead of print] PMID: 25306193
Boonen SE, Mackay DJ, Hahnemann JM, Docherty L, Grønskov K, Lehmann A, Larsen LG, Haemers AP, Kockaerts Y, Dooms L, Vu DC, Ngoc CT, Nguyen PB, Kordonouri O, Sundberg F, Dayanikli P, Puthi V, Acerini C, Massoud AF, Tümer Z, Temple IK
Diabetes Care 2013 Mar;36(3):505-12. Epub 2012 Nov 12 doi: 10.2337/dc12-0700. [Epub ahead of print] PMID: 23150280Free PMC Article
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. [Epub ahead of print] PMID: 23050777Free PMC Article
Iafusco D, Massa O, Pasquino B, Colombo C, Iughetti L, Bizzarri C, Mammì C, Lo Presti D, Suprani T, Schiaffini R, Nichols CG, Russo L, Grasso V, Meschi F, Bonfanti R, Brescianini S, Barbetti F; Early Diabetes Study Group of ISPED
Acta Diabetol 2012 Oct;49(5):405-8. Epub 2011 Sep 28 doi: 10.1007/s00592-011-0331-8. [Epub ahead of print] PMID: 21953423Free PMC Article

Clinical prediction guides

Demirbilek H, Arya VB, Ozbek MN, Houghton JA, Baran RT, Akar M, Tekes S, Tuzun H, Mackay DJ, Flanagan SE, Hattersley AT, Ellard S, Hussain K
Eur J Endocrinol 2015 Jun;172(6):697-705. Epub 2015 Mar 9 doi: 10.1530/EJE-14-0852. [Epub ahead of print] PMID: 25755231Free PMC Article
Alkorta-Aranburu G, Carmody D, Cheng YW, Nelakuditi V, Ma L, Dickens JT, Das S, Greeley SA, del Gaudio D
Mol Genet Metab 2014 Dec;113(4):315-20. Epub 2014 Sep 28 doi: 10.1016/j.ymgme.2014.09.007. [Epub ahead of print] PMID: 25306193
Boonen SE, Mackay DJ, Hahnemann JM, Docherty L, Grønskov K, Lehmann A, Larsen LG, Haemers AP, Kockaerts Y, Dooms L, Vu DC, Ngoc CT, Nguyen PB, Kordonouri O, Sundberg F, Dayanikli P, Puthi V, Acerini C, Massoud AF, Tümer Z, Temple IK
Diabetes Care 2013 Mar;36(3):505-12. Epub 2012 Nov 12 doi: 10.2337/dc12-0700. [Epub ahead of print] PMID: 23150280Free PMC Article
Mackay DJ, Temple IK
Am J Med Genet C Semin Med Genet 2010 Aug 15;154C(3):335-42. doi: 10.1002/ajmg.c.30272. PMID: 20803656
Klupa T, Kozek E, Nowak N, Cyganek K, Gach A, Milewicz T, Czajkowski K, Tolloczko J, Mlynarski W, Malecki MT
J Clin Endocrinol Metab 2010 Aug;95(8):3599-604. Epub 2010 May 13 doi: 10.1210/jc.2010-0096. [Epub ahead of print] PMID: 20466780

Recent systematic reviews

Greeley SA, Tucker SE, Worrell HI, Skowron KB, Bell GI, Philipson LH
Curr Opin Endocrinol Diabetes Obes 2010 Feb;17(1):13-9. doi: 10.1097/MED.0b013e328334f158. PMID: 19952737

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