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Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients

Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients
Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients
AIMS/HYPOTHESIS: 6q24 transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes presenting in the neonatal period that remits during infancy but, in a proportion of cases, recurs in later life. We aim to describe the clinical presentation of 6q24 TNDM in the largest worldwide cohort of patients with defined molecular aetiology, in particular seeking differences in presentation or clinical history between aetiological groups. METHODS: One-hundred and sixty-three patients with positively diagnosed 6q24 TNDM were ascertained from Europe, the Americas, Asia and Australia. Clinical data from referrals were recorded and stratified by the molecular aetiology of patients. RESULTS: 6q24 TNDM patients presented at a modal age of one day, with growth retardation and hyperglycaemia, irrespective of molecular aetiology. There was a positive correlation between age of presentation and gestational age, and a negative correlation between adjusted birthweight SD and age of remission. Congenital anomalies were significantly more frequent in patients with paternal uniparental disomy of chromosome 6 or hypomethylation of multiple imprinted loci defects than in those with 6q24 duplication or isolated hypomethylation defects. Patients with hypomethylation had an excess representation of assisted conception at 15%. CONCLUSIONS/INTERPRETATION: This, the largest case series of 6q24 TNDM published, refines and extends the clinical phenotype of the disorder and confirms its clinical divergence from other monogenic TNDM in addition to identifying previously unreported clinical differences between 6q24 subgroups.
0012-186X
758-762
Docherty, L.E.
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Kabwama, S.
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Lehmann, A.
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Hawke, E.
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Harrison, L.
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Flanagan, S.E.
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Ellard, S.
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Hattersley, A.T.
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Shield, J.P.H.
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Ennis, S.
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Mackay, D.J.G.
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Temple, I.K.
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Docherty, L.E.
4accb565-e53b-400f-8d62-83935e2ae410
Kabwama, S.
9f418ba4-0b40-4d9a-bbb9-ffe153cf51e4
Lehmann, A.
2a783c9a-b9b8-4b7f-b3ac-a0d487f16844
Hawke, E.
80d82790-131b-4617-9749-b70662885640
Harrison, L.
5cfeb2d7-e33a-4963-b93f-bf1bd6694e89
Flanagan, S.E.
1713096d-47b2-427d-980f-3c3450a743dd
Ellard, S.
e83de653-52c7-4706-9ddf-da5047a1cef5
Hattersley, A.T.
c555d835-dd08-415c-be14-26940d5c582d
Shield, J.P.H.
7e45e9e5-0a51-4086-87dc-8d4e2da7e5c8
Ennis, S.
7b57f188-9d91-4beb-b217-09856146f1e9
Mackay, D.J.G.
588a653e-9785-4a00-be71-4e547850ee4a
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226

Docherty, L.E., Kabwama, S., Lehmann, A., Hawke, E., Harrison, L., Flanagan, S.E., Ellard, S., Hattersley, A.T., Shield, J.P.H., Ennis, S., Mackay, D.J.G. and Temple, I.K. (2013) Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients. Diabetologia, 56 (4), 758-762. (doi:10.1007/s00125-013-2832-1). (PMID:23385738)

Record type: Article

Abstract

AIMS/HYPOTHESIS: 6q24 transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes presenting in the neonatal period that remits during infancy but, in a proportion of cases, recurs in later life. We aim to describe the clinical presentation of 6q24 TNDM in the largest worldwide cohort of patients with defined molecular aetiology, in particular seeking differences in presentation or clinical history between aetiological groups. METHODS: One-hundred and sixty-three patients with positively diagnosed 6q24 TNDM were ascertained from Europe, the Americas, Asia and Australia. Clinical data from referrals were recorded and stratified by the molecular aetiology of patients. RESULTS: 6q24 TNDM patients presented at a modal age of one day, with growth retardation and hyperglycaemia, irrespective of molecular aetiology. There was a positive correlation between age of presentation and gestational age, and a negative correlation between adjusted birthweight SD and age of remission. Congenital anomalies were significantly more frequent in patients with paternal uniparental disomy of chromosome 6 or hypomethylation of multiple imprinted loci defects than in those with 6q24 duplication or isolated hypomethylation defects. Patients with hypomethylation had an excess representation of assisted conception at 15%. CONCLUSIONS/INTERPRETATION: This, the largest case series of 6q24 TNDM published, refines and extends the clinical phenotype of the disorder and confirms its clinical divergence from other monogenic TNDM in addition to identifying previously unreported clinical differences between 6q24 subgroups.

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Accepted/In Press date: 6 February 2013
Published date: April 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 348168
URI: http://eprints.soton.ac.uk/id/eprint/348168
ISSN: 0012-186X
PURE UUID: ae395ed7-df56-41f0-a1f7-a160cbb1d2d9
ORCID for S. Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for D.J.G. Mackay: ORCID iD orcid.org/0000-0003-3088-4401
ORCID for I.K. Temple: ORCID iD orcid.org/0000-0002-6045-1781

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Date deposited: 07 Feb 2013 13:53
Last modified: 28 Oct 2023 01:45

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Contributors

Author: L.E. Docherty
Author: S. Kabwama
Author: A. Lehmann
Author: E. Hawke
Author: L. Harrison
Author: S.E. Flanagan
Author: S. Ellard
Author: A.T. Hattersley
Author: J.P.H. Shield
Author: S. Ennis ORCID iD
Author: D.J.G. Mackay ORCID iD
Author: I.K. Temple ORCID iD

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