Sulphonylurea therapy improves cognition in a patient with the V59M KCNJ11 mutation.

BACKGROUND: KCNJ11 mutations are a common cause of diabetes diagnosed in the first 6 months of life, and approximately 25% of patients have neurological features. Sulphonylureas have been shown to improve glycaemic control and also motor function, but the impact on cognitive function has not been extensively addressed previously. METHODS: The patient had a low birth weight and was found to have diabetes at the age of 2 days. The patient was treated with insulin from diagnosis. The child also had marked developmental delay so that his average functional age was 2.5 years when he was 12 years old. A V59M mutation in KCNJ11 was found on sequencing, resulting in a diagnosis of intermediate developmental delay, epilepsy, neonatal diabetes (DEND) syndrome. Identification of a Kir6.2 mutation allowed insulin injections to be replaced by glibenclamide tablets. RESULTS: This resulted not only in improved glycaemic control (HbA(1c) fell from 8.1 to 6.5%), but also an impressive improvement in many aspects of cognitive function, with the functional age increasing to 4 years within 6 months of treatment change. CONCLUSIONS: This is the first clear report of cognitive function improving in a patient with the neurological features associated with a K(ATP) channel mutation following transfer to sulphonylureas. The finding of cognitive improvement suggests that glibenclamide is likely to be acting directly on the brain and not just on nerve and muscle, improving muscle strength.

Evoked potentials in children with chronic renal failure, treated conservatively or by continuous ambulatory peritoneal dialysis.

Children with chronic renal failure (CRF) show developmental, intellectual and motor disturbances. It is questionable if an early start of renal replacement therapy may prevent or delay these disturbances. We studied the neurological and intellectual development of children < 5 years suffering from CRF (creatinine clearance < 20% of normal) prospectively, over a period of 3 years. As part of the neurological study, brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP) were recorded. Measurements were performed in a group of 22 children every 6 months. In 18 of these children CRF was present from birth. Sufficient data were available for analysis in 19 (BAEP) and 22 (SSEP), respectively. A delay of peak I of BAEP gave indications for peripheral conduction disturbances, possibly due to cochlear dysfunction. Brainstem conduction was normal. There were no differences between the children treated conservatively (n = 9) and those treated with continuous ambulatory peritoneal dialysis (CAPD) (n = 10). In children < 2.5 years SSEP showed a delayed thalamocortical conduction, which was not observed in older children. This might indicate a delayed myelination in young children with CRF. No differences were found between the children treated conservatively (n = 10) and those treated with CAPD (n = 12).