ESPE Abstracts (2014) 82 FC9.6

Sulfonylurea Therapy Corrects Hypotonia, Attention Deficits, Improves Complex Neuropsychological Functions and Motricity in Patients with Neonatal Diabetes Secondary to Mutation in Potassium Channel Subunits, Through a CNS Effect

Jacques Beltranda,b, Laurence Vaivre-Douvretb,d, Kanetee Busiaha,b, Emmanuel Fourniere,m, Nathalie Boddaertb,h, Myriam Veraa, Nadia Bahi-Buissonb,i, Emmanuel Bui-Quocf, Isabelle Ingster-Moatig, Isabelle Flechtnera, Albane Simona,l, Raphael Scharfmannc, Helene Cavej, Caroline Eliek & Michel Polaka,b

aService Endocrinologie, Gynécologie et Diabétologie Pédiatrique, Hôpital Universitaire Necker Enfants Malades, Paris, France; bFaculté de Médecine Paris Descartes, Université Sorbonne Paris Cité, Paris, France; cInserm U1016, Institut Cochin, Paris, France; dInserm UMR-S0669, Université Paris Sud et Paris Descartes, Service de Pédopsychiatrie, Paris, France; eCentre de Référence des Canalopathies Musculaires, Hôpital La pitié Salpêtrière, Paris, France; fService d’Ophtalmologie, Hôpital Universitaire Robert Debré, Paris, France; gService d’Ophtalmologie, Hôpital Universitaire Necker Enfants Malades, Paris, France; hService d’Imagerie Médicale, Hôpital Universitaire Necker Enfants Malades, Paris, France; iService de Neurologie Pédiatrique, Hôpital Universitaire Necker Enfants Malades, Paris, France; jService de Génétique, Hôpital Universitaire Robert Debré, Université Denis Diderot, Paris, France; kUnité de Recherche Clinique, Centre d’Investigation Clinique, Hôpital Universitaire Necker Enfants Malades, Paris, France; lService de Pédiatrie, Centre Hospitalier de Versailles, Paris, France; mDépartement de Neurophysiologie Clinique, Université Pierre et Marie Curie, Paris, France

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, 0.1–18.5 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 didn’t 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.

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