Background: Sulfonylurea therapy (SU) allows a better metabolic control than insulin in patients with neonatal diabetes secondary to mutation in potassium channel subunits (ND-K). Most of these patients have neurological and neuromotor developmental impairments whose changes under SU has not been studied in a systematic and prospective way in a large cohort.
Objective and Hypotheses: To demonstrate the beneficial effect of SU on neuropsychological functioning in patients with ND-K.
Method: 18 patients (15 boys, 0.118.5 years). Neurological (MRI, electroencephalogram, electromyography (EMG)) and quantitative neuropsychological and neuropsychomotor evaluations were performed before and 12 months after the switch from insulin to SU.
Results: SU allowed a dramatic improvement of HbA1c (mean, −1.55%; range, −3.8 to 0.1%; P<0.0001). 17 patients presented neuro-motor developmental delay or defect (hypotonia, developmental coordination or attention disorders). One showed pyramidal signs and epilepsy. MRI was abnormal in 12 patients (periventricular white matter abnormalities, multiple punctate white matter or brainstem hyper intensities). At M12, hypotonia was corrected in 12 out 15 affected patients and visual attention deficits in ten out 13. In all patients younger than 3 years (n=8), global motricity impairments were corrected and fine motricity in 3. In older patients (n=10), gesture conception and realization were also improved (two hands praxia improved in four out eight affected patients, imitation of gesture and body spatial integration in six). Motor and sensitive nerve conduction and membrane excitability studies with EMG were normal at baseline and at M12. SU didnt significantly improved intelligence score.
Conclusion: SU therapy in ND-K allows a measurable improvement of neuropsychomotor impairments that seems to be greater in younger patients. EMG shows that it is not a peripheral but rather a central effect. All efforts should be made for an early genetic diagnosis allowing a rapid switch to SU in ND-K.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology