U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from PMC

Diabetes mellitus, transient neonatal, 1(TNDM1)

MedGen UID:
371317
Concept ID:
C1832386
Disease or Syndrome
Synonyms: Chromosome 6-associated transient diabetes mellitus; Diabetes Mellitus, 6q24-Related Transient Neonatal; Diabetes mellitus, transient neonatal; TNDM1
SNOMED CT: Diabetes mellitus, transient neonatal 1 (609579009); TNDM1 (609579009)
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.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Genes (locations): HYMAI (6q24.2); ZFP57 (6p22.1)
 
Monarch Initiative: MONDO:0011073
OMIM®: 601410
Orphanet: ORPHA99886

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 restriction, 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 may be present. 6q24-TNDM associated with a multilocus imprinting disturbance (MLID) can be associated with marked hypotonia, congenital heart disease, deafness, neurologic features including epilepsy, and renal malformations. 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]
Authors:
Isabel Karen Temple  |  Deborah JG Mackay   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 (see PNDM1, 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 MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/6q24-related-transient-neonatal-diabetes-mellitus

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.
Severe failure to thrive
MedGen UID:
343373
Concept ID:
C1855514
Finding
Dehydration
MedGen UID:
8273
Concept ID:
C0011175
Disease or Syndrome
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Transitory neonatal diabetes mellitus
MedGen UID:
449530
Concept ID:
C0342273
Disease or Syndrome
Hyperglycemia in the first month of life due to a genetically determined defect in the structure, secretion and/or function of insulin that resolves spontaneously within nine months of onset.

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. doi: 10.1093/hmg/9.4.589. PMID: 10699182

Recent clinical studies

Etiology

Syding LA, Nickl P, Kasparek P, Sedlacek R
Cells 2020 Apr 16;9(4) doi: 10.3390/cells9040993. PMID: 32316223Free PMC Article
Carli D, Riberi E, Ferrero GB, Mussa A
J Clin Res Pediatr Endocrinol 2020 Mar 19;12(1):1-16. Epub 2019 Apr 10 doi: 10.4274/jcrpe.galenos.2019.2018.0249. PMID: 30968677Free PMC Article
Li X, Xu A, Sheng H, Ting TH, Mao X, Huang X, Jiang M, Cheng J, Liu L
Pediatr Diabetes 2018 Mar;19(2):251-258. Epub 2017 Aug 8 doi: 10.1111/pedi.12560. PMID: 28791793
Bak M, Boonen SE, Dahl C, Hahnemann JM, Mackay DJ, Tümer Z, Grønskov K, Temple IK, Guldberg P, Tommerup N
BMC Med Genet 2016 Apr 14;17:29. doi: 10.1186/s12881-016-0292-4. PMID: 27075368Free PMC Article
Blair HA, Keating GM
Drugs 2016 Mar;76(3):363-74. doi: 10.1007/s40265-016-0541-z. PMID: 26821280

Diagnosis

Perri A, Fattore S, Minucci A, Rinelli M, Barbetti F, Pitocco D, Costa S, Vento G
Mol Biol Rep 2024 Jun 14;51(1):753. doi: 10.1007/s11033-024-09668-2. PMID: 38874636
Carli D, Riberi E, Ferrero GB, Mussa A
J Clin Res Pediatr Endocrinol 2020 Mar 19;12(1):1-16. Epub 2019 Apr 10 doi: 10.4274/jcrpe.galenos.2019.2018.0249. PMID: 30968677Free PMC Article
Li X, Xu A, Sheng H, Ting TH, Mao X, Huang X, Jiang M, Cheng J, Liu L
Pediatr Diabetes 2018 Mar;19(2):251-258. Epub 2017 Aug 8 doi: 10.1111/pedi.12560. PMID: 28791793
Bak M, Boonen SE, Dahl C, Hahnemann JM, Mackay DJ, Tümer Z, Grønskov K, Temple IK, Guldberg P, Tommerup N
BMC Med Genet 2016 Apr 14;17:29. doi: 10.1186/s12881-016-0292-4. PMID: 27075368Free PMC Article
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. PMID: 25755231Free PMC Article

Therapy

Kontbay T, Atar M, Demirbilek H
J Pediatr Endocrinol Metab 2022 May 25;35(5):695-698. Epub 2022 Feb 28 doi: 10.1515/jpem-2021-0538. PMID: 35218690
Coppell K, Freer T, Abel S, Whitehead L, Tipene-Leach D, Gray AR, Merriman T, Sullivan T, Krebs J, Perreault L
BMJ Open 2019 Dec 9;9(12):e033358. doi: 10.1136/bmjopen-2019-033358. PMID: 31822546Free PMC Article
Li X, Xu A, Sheng H, Ting TH, Mao X, Huang X, Jiang M, Cheng J, Liu L
Pediatr Diabetes 2018 Mar;19(2):251-258. Epub 2017 Aug 8 doi: 10.1111/pedi.12560. PMID: 28791793
Iyigun F, Ozcan B, Kulali F, Celik IH, Cetinkaya S, Bas AY, Demirel N
J Trop Pediatr 2017 Oct 1;63(5):399-401. doi: 10.1093/tropej/fmx005. PMID: 28334746
Blair HA, Keating GM
Drugs 2016 Mar;76(3):363-74. doi: 10.1007/s40265-016-0541-z. PMID: 26821280

Prognosis

Kontbay T, Atar M, Demirbilek H
J Pediatr Endocrinol Metab 2022 May 25;35(5):695-698. Epub 2022 Feb 28 doi: 10.1515/jpem-2021-0538. PMID: 35218690
Coppell K, Freer T, Abel S, Whitehead L, Tipene-Leach D, Gray AR, Merriman T, Sullivan T, Krebs J, Perreault L
BMJ Open 2019 Dec 9;9(12):e033358. doi: 10.1136/bmjopen-2019-033358. PMID: 31822546Free PMC Article
Li X, Xu A, Sheng H, Ting TH, Mao X, Huang X, Jiang M, Cheng J, Liu L
Pediatr Diabetes 2018 Mar;19(2):251-258. Epub 2017 Aug 8 doi: 10.1111/pedi.12560. PMID: 28791793
Kamoun T, Chabchoub I, Ben Ameur S, Kmiha S, Aloulou H, Cave H, Polak M, Hachicha M
Arch Pediatr 2017 May;24(5):453-456. Epub 2017 Mar 24 doi: 10.1016/j.arcped.2017.02.021. PMID: 28347637
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. PMID: 25755231Free PMC Article

Clinical prediction guides

Coppell K, Freer T, Abel S, Whitehead L, Tipene-Leach D, Gray AR, Merriman T, Sullivan T, Krebs J, Perreault L
BMJ Open 2019 Dec 9;9(12):e033358. doi: 10.1136/bmjopen-2019-033358. PMID: 31822546Free PMC Article
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. PMID: 25755231Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...