OP61 – 2294: Pantotenate kinase associated neurodegeneration: Clinical assessment and genetic characterization by means of a Spanish multi-centre research network

Abstract

Objective We aimed to design and validate a quantitative method for clinical assessment of pantothenate kinase associated neurodegeneration (PKAN). Methods Cross-sectional multicenter study of PKAN patients recruited through professional associations. Design of a Disease Rating Scale for PKAN (PKAN-DRS) including five sub-scales: cognitive, behavioral, dystonia, parkinsonism, other neurological signs and disability. Items were scored from 0 to 3–4 (maximum severity), (total scores 0–125). For validity and reliability assessment, three independent examiners rated PKAN patients using recorded videotapes. Sanger sequencing of NBIA genes was performed in unsolved NBIA families. Results 13 PKAN patients (mean age 32 years, range 8–77) were assessed through the PKAN-DRS (scores 29–71). Higher scores were obtained in the following items: postural instability, bradikinesia and freezing (parkinson subscale); jaw-tongue, lower face, foot and hand (dystonia subscale); gait and speech (other neurologic signs). Spearman correlation tests showed significant positive correlations between disability and physical scores. Age at diagnosis correlated negatively with dystonia and positively with Parkinsonism. Parkinsonism and disability increased significantly with disease duration. The ICCs for inter-observer agreement was considered “almost perfect” (ICC=0.97), with an internal reliability when all subscales are included considered as “good” (Cronbach's alpha = 0.85). Regarding inter-item evaluation, reliability was considered “good” for dystonia, parkinsonism and disability sub-scores (0.87, 0.82 and 0.88, respectively) and “poor” for other neurological signs (0.20). Six homozygous p. T528M gipsy patients obtained lower PKAN-DRS scores for all subscales when compared with the group of patients with other mutations. Conclusion The proposed PKAN-DRS seems a reliable method to assess the more prevalent neurologic signs in PKAN. Dystonia was more severe in patients with an earlier disease onset, predominating in the jaw and tongue and in the distal limbs. Atypical parkinsonism worsened with disease duration. Haplotype studies are necessary to search for a possible founder effect of the mutation p. T528M in our population.