Dataset Information

Psychiatric morbidity in children with KCNJ11 neonatal diabetes.

ABSTRACT:

Aims

Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the pancreatic KATP channel, cause neonatal diabetes. KCNJ11 is also expressed in the brain, and ~ 20% of those affected have neurological features, which may include features suggestive of psychiatric disorder. No previous studies have systematically characterized the psychiatric morbidity in people with KCNJ11 neonatal diabetes. We aimed to characterize the types of psychiatric disorders present in children with KCNJ11 mutations, and explore their impact on families.

Methods

The parents and teachers of 10 children with neonatal diabetes due to KCNJ11 mutations completed the Strengths and Difficulties Questionnaire and the Development and Wellbeing Assessment. Strengths and Difficulties Questionnaire scores were compared with normative data. Diagnoses from the Development and Wellbeing Assessment were compared with known clinical diagnoses.

Results

Strengths and Difficulties Questionnaire scores indicated high levels of psychopathology and impact. Psychiatric disorder(s) were present in all six children with the V59M or R201C mutation, and the presence of more than one psychiatric disorder was common. Only two children had received a formal clinical diagnosis, with a further one awaiting assessment, and the coexistence of more than one psychiatric disorder had been missed. Neurodevelopmental (attention deficit hyperactivity disorder and autism) and anxiety disorders predominated.

Conclusions

Systematic assessment using standardized validated questionnaires reveals a range of psychiatric morbidity in children with KCNJ11 neonatal diabetes. This is under-recognized clinically and has a significant impact on affected children and their families. An integrated collaborative approach to clinical care is needed to manage the complex needs of people with KCNJ11 neonatal diabetes.

SUBMITTER: Bowman P

PROVIDER: S-EPMC5031218 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Psychiatric morbidity in children with KCNJ11 neonatal diabetes.

Bowman P P Broadbridge E E Knight B A BA Pettit L L Flanagan S E SE Reville M M Tonks J J Shepherd M H MH Ford T J TJ Hattersley A T AT

Diabetic medicine : a journal of the British Diabetic Association 20160521 10

<h4>Aims</h4>Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the pancreatic KATP channel, cause neonatal diabetes. KCNJ11 is also expressed in the brain, and ~ 20% of those affected have neurological features, which may include features suggestive of psychiatric disorder. No previous studies have systematically characterized the psychiatric morbidity in people with KCNJ11 neonatal diabetes. We aimed to characterize the types of psychiatric disorders present in children with KCN ...[more]

PMID: 27086753

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Project description:Aims/hypothesisThe finding that patients with diabetes due to potassium channel mutations can transfer from insulin to sulfonylureas has revolutionised the management of patients with permanent neonatal diabetes. The extent to which the in vitro characteristics of the mutation can predict a successful transfer is not known. Our aim was to identify factors associated with successful transfer from insulin to sulfonylureas in patients with permanent neonatal diabetes due to mutations in KCNJ11 (which encodes the inwardly rectifying potassium channel Kir6.2).MethodsWe retrospectively analysed clinical data on 127 patients with neonatal diabetes due to KCNJ11 mutations who attempted to transfer to sulfonylureas. We considered transfer successful when patients completely discontinued insulin whilst on sulfonylureas. All unsuccessful transfers received ?0.8 mg kg(-1) day(-1) glibenclamide (or the equivalent) for >4 weeks. The in vitro response of mutant Kir6.2/SUR1 channels to tolbutamide was assessed in Xenopus oocytes. For some specific mutations, not all individuals carrying the mutation were able to transfer successfully; we therefore investigated which clinical features could predict a successful transfer.ResultsIn all, 112 out of 127 (88%) patients successfully transferred to sulfonylureas from insulin with an improvement in HbA1c from 8.2% (66 mmol/mol) on insulin, to 5.9% (41 mmol/mol) on sulphonylureas (p?=?0.001). The in vitro response of the mutation to tolbutamide determined the likelihood of transfer: the extent of tolbutamide block was <63% for the p.C166Y, p.I296L, p.L164P or p.T293N mutations, and no patients with these mutations successfully transferred. However, most individuals with mutations for which tolbutamide block was >73% did transfer successfully. The few patients with these mutations who could not transfer had a longer duration of diabetes than those who transferred successfully (18.2 vs 3.4 years, p?=?0.032). There was no difference in pre-transfer HbA1c (p?=?0.87), weight-for-age z scores (SD score; p?=?0.12) or sex (p?=?0.17).Conclusions/interpretationTransfer from insulin is successful for most KCNJ11 patients and is best predicted by the in vitro response of the specific mutation and the duration of diabetes. Knowledge of the specific mutation and of diabetes duration can help predict whether successful transfer to sulfonylureas is likely. This result supports the early genetic testing and early treatment of patients with neonatal diabetes aged under 6 months.

Dataset Information

Psychiatric morbidity in children with KCNJ11 neonatal diabetes.

Aims

Methods

Results

Conclusions

Publications

Psychiatric morbidity in children with KCNJ11 neonatal diabetes.

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