Objective: To analyze the rate of disease progression of PKAN over a 12 year period in 37 patients with genetically-confirmed PKAN in the Dominican Republic.

Background: PKAN is a rare generalized dystonia with recessive inheritance that slowly and relentlessly progresses over time in otherwise developmentally normal children. Carriers of a c.680 A>G mutation of the PANK2 gene are highly prevalent in the Dominican Republic allowing longitudinal follow-up and characterization of the natural course of the disease in a large cohort. Significant phenotypic expression has been observed with varying rates of severity and disease progression, making characterization of said rates relevant for treatment and prognosis.

Method: All patients with genetically-confirmed PKAN and at least two standardized measurements of dystonia severity between the years of 2007-2019 were selected. The rate of disease progression for each patient was calculated by subtracting consecutive score measurements and dividing the result by the time intervals between each measurement. To control for the effects of repeated, correlated, measurements in the same subjects over time and the effects of phenotypic variation between subjects, linear mixed effect model (LMM) was used, with random intercepts and slopes. Estimates were made by restricted maximum likelihood (REML) with an autoregressive (heterogeneous) covariance structure.

Results: Two or more standardized scores with the Fahn-Mardsen (FM) and/or the Unified Dystonia Rating Scale (UDRS) were available for 37 patients at any of four time points (2007, 2010, 2011 and 2019) yielding a total of 105 rated scales and a cumulative measured duration of disease of 307 years. The mean age of onset and duration of disease per subject were 9.7 ± 2.7 and 15.6 ± 9, respectively. The number of valid intervals of the UDRS were 30 with a mean difference of 52.17 ± 29 and of the FM 32 with a mean difference of 34.28 ± 32.4. The average rate of disease progression as assessed by the UDRS was 13.3 points per year and by the FM 15.5 per year.

Conclusion: Based on longitudinal measurements with standardized instruments, the average rate of progression of PKAN in the Dominican Republic is 13.3 and 15.5 points per year on the UDRS and FM, respectively.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-analysis-of-disease-progression-in-a-large-pkan-cohort-in-the-dominican-republic/