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Clinical and genetic features of Argentinian children with diabetes-onset before 12 months of age: successful transfer from insulin to oral sulfonylurea

Clinical and genetic features of Argentinian children with diabetes-onset before 12 months of age: successful transfer from insulin to oral sulfonylurea
Clinical and genetic features of Argentinian children with diabetes-onset before 12 months of age: successful transfer from insulin to oral sulfonylurea
Aims   Neonatal diabetes mellitus (NDM) is a rare monogenic disorder, reported to affect less than 2 cases per 100,000 infants. There are two types, permanent (PNDM) and transient (TNDM). We describe our clinical experience in determining and comparing the genetic basis of diabetes in children with onset before 6 months versus those diagnosed between 6 and 12 months of age.
Methods   We reviewed medical records of children with diabetes diagnosed before 12 months of age. Genetic testing was performed in all cases.
Results   12 patients were diagnosed with diabetes before 6 months of age (PNDM = 6; TNDM = 6), and 11 patients between 6 and 12 months (all with permanent diabetes). Among children with PNDM, we identified three different KCNJ11 mutations in 5 patients, and one novel ABCC8 mutation in a single patient. Among children with TNDM, we detected a KCNJ11 and ABCC8 mutation each in a single patient and methylation abnormalities at chromosome 6q24 in 4 patients.
Among children with diabetes diagnosed between 6 and 12 months, 1 patient had an INS mutation and one patient was homozygous for an SLC19A2 mutation which confirmed a diagnosis of thiamine-responsive megaloblastic anaemia syndrome. Five of the patients with an ABCC8 or KCNJ11 mutation have successfully transferred from insulin to glibenclamide whist 1 child demonstrated a partial response to sulfonylurea treatment.
Conclusions   Investigating the underlying genetic basis of diabetes in children with onset before 1 year is useful for choosing the most efficient treatment, the basis of Personalized Medicine.
0168-8227
104-110
Taberner, Patricia
b8725b35-f7f2-4122-a527-c892b355b53d
Flanagan, Sarah E.
ad5fb709-7f4b-4063-9b9f-bdf9c1cf1d2b
Mackay, Deborah J.
588a653e-9785-4a00-be71-4e547850ee4a
Ellard, Sian
6c9b0ede-8980-4602-b063-444b165baa09
Taverna, Mariano J.
699899cd-1706-496c-a47e-c8f2597df6f9
Ferraro, Mabel
889079f0-f458-42c0-8660-f43af4727d4a
Taberner, Patricia
b8725b35-f7f2-4122-a527-c892b355b53d
Flanagan, Sarah E.
ad5fb709-7f4b-4063-9b9f-bdf9c1cf1d2b
Mackay, Deborah J.
588a653e-9785-4a00-be71-4e547850ee4a
Ellard, Sian
6c9b0ede-8980-4602-b063-444b165baa09
Taverna, Mariano J.
699899cd-1706-496c-a47e-c8f2597df6f9
Ferraro, Mabel
889079f0-f458-42c0-8660-f43af4727d4a

Taberner, Patricia, Flanagan, Sarah E., Mackay, Deborah J., Ellard, Sian, Taverna, Mariano J. and Ferraro, Mabel (2016) Clinical and genetic features of Argentinian children with diabetes-onset before 12 months of age: successful transfer from insulin to oral sulfonylurea. Diabetes Research and Clinical Practice, 117, 104-110. (doi:10.1016/j.diabres.2016.04.005). (PMID:27329029)

Record type: Article

Abstract

Aims   Neonatal diabetes mellitus (NDM) is a rare monogenic disorder, reported to affect less than 2 cases per 100,000 infants. There are two types, permanent (PNDM) and transient (TNDM). We describe our clinical experience in determining and comparing the genetic basis of diabetes in children with onset before 6 months versus those diagnosed between 6 and 12 months of age.
Methods   We reviewed medical records of children with diabetes diagnosed before 12 months of age. Genetic testing was performed in all cases.
Results   12 patients were diagnosed with diabetes before 6 months of age (PNDM = 6; TNDM = 6), and 11 patients between 6 and 12 months (all with permanent diabetes). Among children with PNDM, we identified three different KCNJ11 mutations in 5 patients, and one novel ABCC8 mutation in a single patient. Among children with TNDM, we detected a KCNJ11 and ABCC8 mutation each in a single patient and methylation abnormalities at chromosome 6q24 in 4 patients.
Among children with diabetes diagnosed between 6 and 12 months, 1 patient had an INS mutation and one patient was homozygous for an SLC19A2 mutation which confirmed a diagnosis of thiamine-responsive megaloblastic anaemia syndrome. Five of the patients with an ABCC8 or KCNJ11 mutation have successfully transferred from insulin to glibenclamide whist 1 child demonstrated a partial response to sulfonylurea treatment.
Conclusions   Investigating the underlying genetic basis of diabetes in children with onset before 1 year is useful for choosing the most efficient treatment, the basis of Personalized Medicine.

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More information

Accepted/In Press date: 18 April 2016
e-pub ahead of print date: 26 April 2016
Published date: July 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 398649
URI: http://eprints.soton.ac.uk/id/eprint/398649
ISSN: 0168-8227
PURE UUID: a02d4b0e-f392-4cef-b2e2-8a3b3700f6da
ORCID for Deborah J. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

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Date deposited: 29 Jul 2016 13:15
Last modified: 07 Oct 2020 01:43

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Contributors

Author: Patricia Taberner
Author: Sarah E. Flanagan
Author: Sian Ellard
Author: Mariano J. Taverna
Author: Mabel Ferraro

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