Abstract
BackgroundGain-of-function mutations in the ATP-sensitive potassium channel can cause permanent neonatal diabetes mellitus (PNDM) or neonatal diabetes accompanied by a constellation of neurological symptoms (iDEND syndrome). Studies of a mouse model of iDEND syndrome revealed that cerebellar Purkinje cell electrical activity was impaired and that the mice exhibited poor motor coordination. In this study, we probed the hand-eye coordination of PNDM and iDEND patients using visual tracking tasks to see if poor motor coordination is also a feature of the human disease.MethodsControl participants (n = 14), patients with iDEND syndrome (n = 6 or 7), and patients with PNDM (n = 7) completed three computer-based tasks in which a moving target was tracked with a joystick-controlled cursor. Patients with PNDM and iDEND were being treated with sulphonylurea drugs at the time of testing.ResultsNo differences were seen between PNDM patients and controls. Patients with iDEND syndrome were significantly less accurate than controls in two of the three tasks. The greatest differences were seen when iDEND patients tracked blanked targets, i.e. when predictive tracking was required. In this task, iDEND patients incurred more discrepancy errors (p = 0.009) and more velocity errors (p = 0.009) than controls.ConclusionsThese results identify impaired hand-eye coordination as a new clinical feature of iDEND. The aetiology of this feature is likely to involve cerebellar dysfunction. The data further suggest that sulphonylurea doses that control the diabetes of these patients may be insufficient to fully correct their neurological symptoms.
Highlights
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels are important metabolic sensors that link cell metabolism to electrical activity in neurones, pancreatic beta-cells and many other cell types [1]
Gain-of-function mutations in either the Kir6.2 (KCNJ11) or SUR1 (ABCC8) subunits of the channel that impair the inhibitory effects of ATP cause a rare genetic form of diabetes that presents shortly after birth
The neurological symptoms have not yet been fully characterised, and other problems may be present. The diabetes of both permanent neonatal diabetes mellitus (PNDM) and iDEND patients is well controlled by oral sulphonylurea drugs, which close KATP channels
Summary
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels are important metabolic sensors that link cell metabolism to electrical activity in neurones, pancreatic beta-cells and many other cell types [1]. They do so by sensing changes in intracellular nucleotides such as ATP, which closes the channel and reduces the KATP current. The neurological symptoms have not yet been fully characterised, and other problems may be present The diabetes of both PNDM and iDEND patients is well controlled by oral sulphonylurea drugs, which close KATP channels. Gain-of-function mutations in the ATP-sensitive potassium channel can cause permanent neonatal diabetes mellitus (PNDM) or neonatal diabetes accompanied by a constellation of neurological symptoms (iDEND syndrome). We probed the hand-eye coordination of PNDM and iDEND patients using visual tracking tasks to see if poor motor coordination is a feature of the human disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
