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Transient neonatal diabetes mellitus 1

Transient neonatal diabetes mellitus is caused by overexpression of a gene cluster at 6q24. These genes are paternally imprinted, so imprinting defects, duplications and ZFP57 mutations can cause such an overexpression. Patients develop abnormalities antenatally. The diabitis starts at one week of age and lasts for about 3 month.

Clinical Findings

Clinical symptoms begin with severe intrauterine growth retardation, macroglossia, and umbilical hernia. In children with ZFP57 mutations additional clinical symptoms may be present. These include structural brain abnormalities, developmental delay, and congenital heart disease.

Diabetes mellitus depelops with 1 week of age but hight blood glucose is measurable immediatly after birth. Initially the patient may require insulin, but after on average 6 month, this is no longer necessary and after about 18 month all abnormalities of glucose metabolism almost disappear. They may reappear in children during infections or in women during pregnancies. These patient more frequently develop type 2 diabetes.


40% of cases are caused by paternal uniparental disomy of chromosome 6 (UPD6). The same percentage is caused by paternal duplication of 6q24. About 20% are caused by hypomethylation of the maternal PLAGL1/HYMAI DMR. Half of the latter cases bear a pathogenetic mutation of the ZFP57 gene.


Neonatal diabetes mellitus
Mitchell-Riley syndrome
Neonatal diabetes mellitus with congenital hypothyroidism
Pancreatogenic diabetes
Permanent neonatal diabetes mellitus
Rabson-Mendenhall syndrome
Renal cysts and diabetes (RCAD)
Transient neonatal diabetes mellitus 1
Transient neonatal diabetes mellitus 2
Transient neonatal diabetes mellitus 3
X-linked immunodysregulation, polyendocrinopathy, and enteropathy



Suzuki S et al. (2007) Molecular basis of neonatal diabetes in Japanese patients.


Arima T et al. (2001) A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus.


Temple IK et al. (1996) Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23.


Mackay DJ et al. (2008) Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57.


None (2000) Neonatal diabetes: new insights into aetiology and implications.


Arthur EI et al. () Transient neonatal diabetes mellitus in a child with invdup(6)(q22q23) of paternal origin.


Gardner RJ et al. (1999) Localisation of a gene for transient neonatal diabetes mellitus to an 18.72 cR3000 (approximately 5.4 Mb) interval on chromosome 6q.


Gardner RJ et al. (2000) An imprinted locus associated with transient neonatal diabetes mellitus.


Marquis E et al. (2000) Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6.


Das S et al. (2000) Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, macroglossia, and craniofacial abnormalities.


Temple IK et al. (2002) Transient neonatal diabetes, a disorder of imprinting.


Ma D et al. (2004) Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM.


Mackay DJ et al. (2005) Bisulphite sequencing of the transient neonatal diabetes mellitus DMR facilitates a novel diagnostic test but reveals no methylation anomalies in patients of unknown aetiology.


Kant SG et al. (2005) Monozygous triplets discordant for transient neonatal diabetes mellitus and for imprinting of the TNDM differentially methylated region.


Mackay DJ et al. (2006) Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus.


Mackay DJ et al. (2006) A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus.


Diatloff-Zito C et al. (2007) Genetic and epigenetic defects at the 6q24 imprinted locus in a cohort of 13 patients with transient neonatal diabetes: new hypothesis raised by the finding of a unique case with hemizygotic deletion in the critical region.


Flanagan SE et al. (2007) Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood.


Ferguson AW et al. (1970) Transient neonatal diabetes mellitus in sibs.


Hurst LD et al. (1997) Growth effects of uniparental disomies and the conflict theory of genomic imprinting.


Christian SL et al. (1999) Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus.


Gardner RJ et al. (1998) Paternal uniparental disomy of chromosome 6 and transient neonatal diabetes mellitus.


OMIM.ORG article

Omim 601410 [^]

Orphanet article

Orphanet ID 99886 [^]
Update: May 10, 2019
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