Hereditary Spastic Paraplegia: Characterization of an Albertan Cohort (P6.010)

OBJECTIVE: To identify families with Hereditary spastic paraplegias (HSP), create a clinical registry and genomic DNA bank to screen for known and novel mutations. BACKGROUND: HSP are rare neurological disorders with onset from early childhood to late adulthood, inherited as autosomal dominant (AD), autosomal recessive (AR) or X-linked (XR) traits with over 50 identified genes. HSP is classified as uncomplicated or complicated. Prevalence is estimated at 5 per 100,000, but epidemiological data is scarce and misdiagnosis common. DESIGN/METHODS: Participants were recruited through Neurogenetic and Neuromuscular clinics in Alberta, and assessed yearly by Spastic Paraplegia Rating Scale and SPATAX-EUROSPA disability score. DNA will be sent for exome sequencing to McGill University (Dr. G.Rouleau), as part of a Canadian consortium. RESULTS: 49 families with 64 patients (36 men and 28 women) have been identified. Thirty one patients (48[percnt]) have a positive family history, with AD inheritance in 18 families (37[percnt]), AR (9 families) and XR (4 families). Eighteen families (37[percnt]) had sporadic HSP. Mean age of onset for AD was 36 years, sporadic 32 years, AR 11 years and XR 1.5 years. Complicated HSP was seen in 27 patients (46[percnt]). Abnormalities among complicated patients include dysarthria (n=19), sensory deficits (n=17), occulomotor abnormalities (n=14), ataxia (n=17), amyotrophy (n=12), dysphagia (n=9), cognitive deficits (n=11) and peripheral neuropathy (n=8). Neuroimaging was abnormal in 9 patients. Thirty four patients (53[percnt]) had SPATAX-EUROSPA disability stage of 3 or more (moderate to severe functional handicap). Results of genetic testing are pending. CONCLUSIONS: This is the first comprehensive population based study looking at all forms of HSP. Prevalence is 2 per 100000. This lower than expected rate could be due to either incomplete ascertainment or lower prevalence in this population. The most common mode of inheritance was AD with almost 50[percnt] having the complicated form. Disclosure: Dr. Venkitachalam has nothing to disclose. Dr. McKenzie has nothing to disclose. Dr. Ashtiani has nothing to disclose. Dr. Huculak has nothing to disclose. Dr. MacLaren has nothing to disclose. Honoraium from UpToDate,