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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, 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

Definition

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 GTR]

Additional descriptions

From GeneReviews
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.  https://www.ncbi.nlm.nih.gov/books/NBK1534
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.  https://ghr.nlm.nih.gov/condition/6q24-related-transient-neonatal-diabetes-mellitus

Clinical features

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.(NICHD)
Intrauterine growth retardation
MedGen UID:
473406
Concept ID:
C1386048
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
Abnormally high BLOOD GLUCOSE level.
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.(NICHD)
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.(NICHD)

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

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
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. PMID: 23150280Free PMC Article

Diagnosis

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
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. PMID: 23150280Free PMC Article

Prognosis

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. PMID: 23150280Free PMC Article

Clinical prediction guides

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. PMID: 23150280Free PMC Article

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