SPAX1 is a neurodegenerative disorder that results in gait disturbances, spastic paraplegia, dysarthria, hyperreflexia, dystonia, pes cavus, head jerks and memory loss. Affected individuals also suffer from ocular anomalies such as slow saccades, supranuclear gaze palsy and ptosis. The disorder has an onset between 10 and 20 years of age. It is slowly progressive and patients may become wheelchair-bound later in life. However, the condition does not affect life span or cognition. The disease varies in severity, even within affected members of the same family. While the global rate of incidence of the condition is unknown, it is found to be highly prevalent in the Canadian region of Newfoundland.
The disorder follows an autosomal dominant pattern of inheritance and is caused by mutations in the VAMP1 gene. This gene encodes an integral membrane protein involved in vesicle fusion and neuronal exocytosis. Recent studies have also found instances of SPAX1 affected individuals with homozygous VAMP1 mutations.
Diagnosis of SPAX1 is made based on clinical features and molecular analysis of the Vesicle-Associated Membrane Protein 1 (VAMP1) gene. There is currently no cure for SPAX1. However, several treatment methods are available that provide symptomatic support, such as baclofen, tizanidine, diazepam and clonazepam. Patients also benefit from physical and occupational therapy.