Juvenile ALS with long-term survival associated with spastin gene mutation

Background: Juvenile ALS (JALS) is a form of chronic motor neuron disease presenting with upper and lower motor neuron symptoms prior to the age of 25 years. Rare cases of JALS with a survival of more than three decades have been described. Genetic risk factors of sporadic JALS are largely unknown.

Objective: to describe a male patient with apparently sporadic JALS at the age of 72 years with a natural history of ALS for 48 years.

Design: a case report, magnetic resonance imaging of the brain and mutation analysis of the spastic gene (SPG4).

Result: at the age of 24 years the patient developed a progressive lower motor neuron syndrome of the left hand followed by paresis and atrophy of the distal left lower limb. In the course of 2 years he showed a pyramidal syndrome of all extremities and a progressive bulbar and pseudobulbar syndrome. Since then he has fulfilled the diagnostic criteria for definite ALS. To date magnetic resonance imaging demonstrated a previously undescribed occipital, parietal and insular atrophy in decreasing order. Mutation screening of the spastin gene identified a heterozygous in-frame insertion within exon 1 coding for two additional amino acids (ins102SerAla).

Conclusion: We report the first case of ALS demonstrating a mutation in the spastin gene. We propose that sequence variants of spastin might serve as a previously unknown genetic risk factor for JALS. It is conceivable that spastin-related hereditary spastic paraplegia may be allelic to ALS with prolonged survival.