Prematurity and genetic testing for neonatal diabetes
Prematurity and genetic testing for neonatal diabetes
BACKGROUND: Hyperglycemia in premature infants is usually thought to reflect inadequate pancreatic development rather than monogenic neonatal diabetes. No studies, to our knowledge, have investigated the prevalence of monogenic forms of diabetes in preterm infants.
METHODS: We studied 750 patients with diabetes diagnosed before 6 months of age. We compared the genetic etiology and clinical characteristics of 146 preterm patients born <37 weeks and compared them with 604 born ?37 weeks.
RESULTS: A genetic etiology was found in 97/146 (66%) preterm infants compared with 501/604 (83%) born ?37weeks, P < .0001. Chromosome 6q24 imprinting abnormalities (27% vs 12%, P = .0001) and GATA6 mutations (9% vs 2%, P = .003) occurred more commonly in preterm than term infants while mutations in KCNJ11 were less common (21 vs 34%, P = .008). Preterm patients with an identified mutation were diagnosed later than those without an identified mutation (median [interquartile range] 35 [34 to 36] weeks vs 31 [28 to 36] weeks, P < .0001). No difference was seen in other clinical characteristics of preterm patients with and without an identified mutation including age of presentation, birth weight, and time to referral.
CONCLUSIONS: Patients with neonatal diabetes due to a monogenic etiology can be born preterm, especially those with 6q24 abnormalities or GATA6 mutations. A genetic etiology is more likely in patients with less severe prematurity (>32 weeks). Prematurity should not prevent referral for genetic testing as 37% have a potassium channel mutation and as a result can get improved control by replacing insulin with sulphonylurea therapy.
1-9
Besser, R.E.J.
a3a3f059-d3b4-4c05-b305-e61d1a9c4198
Flanagan, S.E.
1713096d-47b2-427d-980f-3c3450a743dd
Mackay, D.G.J.
588a653e-9785-4a00-be71-4e547850ee4a
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Shepherd, M.H.
984b3baa-2eef-4c18-9082-91d00cb61c3a
Shields, B.M.
9bda2f85-4434-4dd8-9f3d-03b051785c4f
Ellard, S.
e83de653-52c7-4706-9ddf-da5047a1cef5
Hattersley, A.T.
c555d835-dd08-415c-be14-26940d5c582d
September 2016
Besser, R.E.J.
a3a3f059-d3b4-4c05-b305-e61d1a9c4198
Flanagan, S.E.
1713096d-47b2-427d-980f-3c3450a743dd
Mackay, D.G.J.
588a653e-9785-4a00-be71-4e547850ee4a
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Shepherd, M.H.
984b3baa-2eef-4c18-9082-91d00cb61c3a
Shields, B.M.
9bda2f85-4434-4dd8-9f3d-03b051785c4f
Ellard, S.
e83de653-52c7-4706-9ddf-da5047a1cef5
Hattersley, A.T.
c555d835-dd08-415c-be14-26940d5c582d
Besser, R.E.J., Flanagan, S.E., Mackay, D.G.J., Temple, I.K., Shepherd, M.H., Shields, B.M., Ellard, S. and Hattersley, A.T.
(2016)
Prematurity and genetic testing for neonatal diabetes.
Pediatrics, 138 (3), .
(doi:10.1542/peds.2015-3926).
(PMID:27540106)
Abstract
BACKGROUND: Hyperglycemia in premature infants is usually thought to reflect inadequate pancreatic development rather than monogenic neonatal diabetes. No studies, to our knowledge, have investigated the prevalence of monogenic forms of diabetes in preterm infants.
METHODS: We studied 750 patients with diabetes diagnosed before 6 months of age. We compared the genetic etiology and clinical characteristics of 146 preterm patients born <37 weeks and compared them with 604 born ?37 weeks.
RESULTS: A genetic etiology was found in 97/146 (66%) preterm infants compared with 501/604 (83%) born ?37weeks, P < .0001. Chromosome 6q24 imprinting abnormalities (27% vs 12%, P = .0001) and GATA6 mutations (9% vs 2%, P = .003) occurred more commonly in preterm than term infants while mutations in KCNJ11 were less common (21 vs 34%, P = .008). Preterm patients with an identified mutation were diagnosed later than those without an identified mutation (median [interquartile range] 35 [34 to 36] weeks vs 31 [28 to 36] weeks, P < .0001). No difference was seen in other clinical characteristics of preterm patients with and without an identified mutation including age of presentation, birth weight, and time to referral.
CONCLUSIONS: Patients with neonatal diabetes due to a monogenic etiology can be born preterm, especially those with 6q24 abnormalities or GATA6 mutations. A genetic etiology is more likely in patients with less severe prematurity (>32 weeks). Prematurity should not prevent referral for genetic testing as 37% have a potassium channel mutation and as a result can get improved control by replacing insulin with sulphonylurea therapy.
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Accepted/In Press date: 14 June 2016
e-pub ahead of print date: 1 September 2016
Published date: September 2016
Organisations:
Human Development & Health
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Local EPrints ID: 399864
URI: http://eprints.soton.ac.uk/id/eprint/399864
ISSN: 0031-4005
PURE UUID: 9ed19ad8-58dc-46b1-adcc-d1ca3a7059e8
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Date deposited: 02 Sep 2016 09:10
Last modified: 15 Mar 2024 03:01
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Contributors
Author:
R.E.J. Besser
Author:
S.E. Flanagan
Author:
M.H. Shepherd
Author:
B.M. Shields
Author:
S. Ellard
Author:
A.T. Hattersley
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