Objective: To investigate the frequency of autosomal recessive paraplegin mutations in patients with sporadic adult-onset upper motor neuron (UMN) syndromes.
Methods: We analyzed the paraplegin gene in 98 Dutch patients with a sporadic adult-onset UMN syndrome. Inclusion criteria were a progressive UMN syndrome, adult onset, duration >6 months, and negative family history. Exclusion criteria were clinical or electrophysiologic evidence of lower motor neuron loss and evidence of other causes using a predefined set of laboratory tests, including analysis of the spastin gene.
Results: Seven patients had homozygous or compound heterozygous pathogenic paraplegin mutations: six patients had UMN symptoms restricted to the legs and one had UMN symptoms in legs and arms. No mutations were found in the 33 patients with UMN involvement of the bulbar region. Age at onset was lower in the seven patients with paraplegin mutations (37 years, range 34-42) than in the 91 patients without mutations (51 years, range 18-77, p = 0.001). Three of the seven patients with paraplegin mutations and none of the patients without mutations developed cerebellar signs during follow-up.
Conclusions: Paraplegin mutations are a frequent cause of sporadic spastic paraparesis.