Patients with KCNJ11-related diabetes frequently have neuropsychological impairments compared with sibling controls.

AIMS: KCNJ11-related diabetes is the most common form of permanent neonatal diabetes and has been associated with a spectrum of neurodevelopmental problems. We compared neurodevelopmental outcomes in patients with KCNJ11 mutations and their sibling controls. METHODS: Through our Monogenic Diabetes Registry (http://monogenicdiabetes.uchicago.edu/), we evaluated 23 patients with KCNJ11 mutations with (n = 9) and without (n = 14) global developmental delay successfully treated with sulfonylurea and 20 healthy sibling controls, using a battery of targeted neuropsychological and behavioural assessments with scaled scores that are comparable across a wide range of ages. RESULTS: Patients with KCNJ11-related diabetes without global developmental delay had significant differences compared with sibling controls on a range of assessments including IQ, measures of academic achievement and executive function. KCNJ11 patients with global delay exhibited significant differences in behavioural symptoms with a tendency to avoid social contact and displayed a reduced ability to adapt to new circumstances. Parents reported more immature behaviour, gross mood swings, bizarre thoughts, other unusual and severe behaviours, and there were also significant deficits in all subdomains of daily living skills. CONCLUSIONS: This series represents the largest and most comprehensive study of neuropsychological and behavioural dysfunction of individuals with KCNJ11 diabetes and is the first to compare outcome with sibling controls. Our data demonstrate the variety of neurodevelopmental problems seen in those with KCNJ11 mutations, even in those without recognized global developmental delays. These data can be used to counsel families and guide structured neurodevelopmental assessments and treatments based on the initial genetic diagnosis in patients with neonatal diabetes.

Adolescent non-adherence reveals a genetic cause for diabetes.

BACKGROUND: Glucokinase related maturity-onset diabetes of the young (GCK-MODY) is a form of monogenic diabetes characterized by mildly elevated fasting blood sugars and HbA(1c) typically ranging from 38 to 60 mmol/mol (5.6-7.6%). It is frequently unrecognized or misdiagnosed as Type 1 or Type 2 diabetes, resulting in unnecessary pharmacologic therapy. CASE REPORT: Two brothers were initially diagnosed with Type 1 diabetes mellitus. The brothers were maintained on a total daily insulin dose of 0.3-0.5 units/kg/day and had HbA(1c) values of 40-51 mmol/mol (5.8-6.8%) throughout childhood. After over 10 years of insulin treatment, the younger brother chose to discontinue his insulin therapy without informing his family or his clinician. Following cessation of insulin treatment, he did not experience any change in overall glycaemic control. Subsequent research-based genetic testing revealed a deleterious mutation in GCK in both brothers (p.Val182Met). The older brother subsequently discontinued insulin therapy and both have remained off all pharmacological therapy with good glycaemic control (HbA(1c) < 53 mmol/mol, < 7%) and no adverse complications. The family was advised to seek confirmatory genetic testing in the father and other relatives with hyperglycaemia. CONCLUSION: The family described above exemplifies the rationale behind considering a genetic cause when evaluating every person with new-onset hyperglycaemia or those with atypical diabetes. The cost of genetic testing for the most common MODY causing genes may be offset by savings made in therapeutic costs. It is important that all clinicians supervising diabetes care recognize the cardinal features that distinguish GCK-MODY from other forms of diabetes.