Pervasive Neuromuscular Deficits in Adults with Nephropathic Cystinosis (S46.008)

Objective: To further characterize myopathy and dysphagia in patients with nephropathic cystinosis. Background: Nephropathic cystinosis is a lysosomal storage disorder that often leads to renal failure by age 10. Prolonged patient survival following renal transplantation has revealed late-onset systemic complications including the development of distal myopathy and dysphagia. Design/Methods: We evaluated 20 patients with nephropathic cystinosis (age: median 28.5, range 20–64) using patient-reported (the M. D. Anderson Dysphagia Inventory (MDADI) and Eating Assessment Tool (EAT-10)) and clinicometric (grip myometry, maximum expiratory pressure, and peak airflow) outcomes. We used Rasch analysis for psychometric evaluation of patient-reported outcome measures and investigated the relationship between strength, swallowing and breathing measures. To succinctly capture muscle weakness, we developed a distal myopathy function scale for nephropathic cystinosis (DMNC). Results: Interim analysis demonstrates that patients self-report problems across several neurological domains: weakness (80%), pain (70%), vision (60%), swallowing (60%), sleep (50%), speech (30%), and breathing (30%). Weakness affected upper more than lower extremities and was adequately represented and weighted on the DMNC. Interestingly, all patients displayed greater degrees of impairment on objective testing than they self-reported. On clinicometric testing, all patients showed weakness in the distal upper extremities (mean grip strength of 23.2 ± 16.6 kilograms-force), all patients had mildly impaired coordination (9-hole peg test mean 24.5 ± 6.5 seconds), and 29% had measurable evidence of aspiration. There were significant correlations between MDADI, EAT-10 and DMNC. There was significant variation in grip myometry among patients who had trouble swallowing. Conclusions: Distal upper, more than lower, extremity muscle weakness and dysphagia are relatively common in patients with nephropathic cystinosis, even in patients not reporting symptoms. We propose new psychometrically-advised patient-reported outcome measures for distal myopathy and dysphagia in patients with nephropathic cystinosis but emphasize the need for quantifiable measures as many patients do not experience or report the degree of neurological impairment. Study Supported by: Cystinosis Research Foundation Disclosure: Dr. Sadjadi has nothing to disclose. Dr. Sullivan has nothing to disclose. Dr. Duong has nothing to disclose. Dr. Corre has nothing to disclose. Dr. James has nothing to disclose. Dr. Eichler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Vertex Pharmaceuticals, Minoryx Therapeutics, Orpheris. Dr. Eichler holds stock and/or stock options in Johnson and Johnson. Dr. Eichler has received research support from Alexion; Retrophin; Neurovia; Applied Genetic Technologies Corp; Bluebird Bio.