Al-Saif et al. (2011) reported a consanguineous Saudi Arabian family in which 6 individuals had early-childhood onset of a neurologic disorder consistent with juvenile ALS, according to the El Escorial criteria (Brooks, 1994). Lower limb spasticity with hyperreflexia ... Al-Saif et al. (2011) reported a consanguineous Saudi Arabian family in which 6 individuals had early-childhood onset of a neurologic disorder consistent with juvenile ALS, according to the El Escorial criteria (Brooks, 1994). Lower limb spasticity with hyperreflexia and weakness were noted at the age of 1 to 2 years. By age 9 or 10, affected individuals showed weakness of the hand and forearm muscles, which progressed to paralysis of the forearm extensors and triceps. By the age of 20 years, 2 patients used wheelchairs. None of the patients had respiratory or bulbar muscle weakness, and sensory and cerebellar functions were normal. Neurophysiologic tests showed evidence of denervation and reinnervation in limb muscles; motor unit potentials were enlarged, polyphasic, and fast firing, with normal sensory nerve action potentials and somatosensory evoked potentials. Brain imaging did not reveal any abnormalities, and cognition was preserved.
By homozygosity mapping followed by candidate gene sequencing, Al-Saif et al. (2011) identified a homozygous pathogenic mutation in the SIGMAR1 gene (601978.0001) in affected members of a consanguineous Saudi Arabian family with early-childhood onset of ALS.