Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of motor neurons in the motor cortex, brainstem, and spinal cord. Over 60% of patients die from respiratory failure within three years of presentation. We report two ALS patients carrying the p.H46R missense mutation in the SOD1 gene presented with a characteristic clinical phenotype of very slow progression. We also reviewed the 13 pedigrees harbouring the p.H46R mutation reported previously. SOD1 p.H46R mutation is consistently associated with a specific phenotype, i.e. lower limb onset with rare bulbar involvement, and a slow progression with longer survival. It is important to recognize the typical clinical picture of the SOD1 p.H46R mutation, and SOD1 sequencing may be necessary to give the patient correct diagnosis and prognosis.
Keywords: Amyotrophic lateral sclerosis; H46R; SOD1 mutation.