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Juvenile amyotrophic lateral sclerosis
Juvenile amyotrophic lateral sclerosis (JALS) is a very rare severe motor neuron disease characterized by progressive upper and lower motor neuron degeneration causing facial spasticity, dysarthria, and gait disorders with onset before 25 years of age.
ORPHA:300605Classification level: Disorder
The prevalence and incidence of JALS are not known. A small number of cases have been reported to date. The disorder has been described in various ethnic groups.
Onset is during childhood with a mean age of 6.5 years and a reported range of 3 to 20 years. Patients then develop motor neuron degeneration leading to facial muscle spasticity, spastic dysarthria, and spastic gait. Some patients are reported to have uncontrolled laughter and weeping (pseudobulbar syndrome). Mild atrophy of the legs and hands are observed in some cases. Bladder dysfunction and sensory disturbances are also found. The disease is usually slowly progressive and some patients have been reported to have become bedridden by 12 to 50 years of age.
Mutations in the following genes have been found in patients presenting with JALS: ALS2 (2q33-q35), and rarely SIGMAR1 (9p13.3), SPG11 (15q13-q15) and FUS (16p11.2). Mutations in the latter gene are sporadic and appear to be associated with a severe and aggressive course.
Diagnosis is based on the clinical findings. Motor evoked potential studies show absent or reduced action potentials, electromyography demonstrates signs of denervation, while nerve conduction velocities are normal. Magnetic resonance imaging (MRI) scans of the brain and spinal cord are normal.
Differential diagnoses include juvenile primary lateral sclerosis and, to a lesser extent, infantile-onset ascending hereditary spastic paralysis (see these terms).
Cases related to the ALS2 and SIGMAR1 genes have an autosomal recessive pattern of inheritance. Genetic counseling should be provided to affected families.
Management and treatment
There is currently no specific treatment. Management primarily involves physical and occupational therapy to promote mobility and independence.
Prognosis is guarded and quality of life severely affected by the clinical manifestations of the disease.