2018 Volume 35 Issue 3 Pages 327-331
A novel ALS (amyotrophic lateral sclerosis)/spinocerebellar ataxia (SCA) crossroad mutation Asidan shows characteristic clinical features was first reported by us in 2000 (Manabe et al.) and 2007 (Ohta et al.). Asidan is also called SCA36, and is caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene (Kobayashi H, Abe K et al., 2011). Clinical, genetic, neuropathologic, and neuroradiologic characteristics of 29 Asidan patients were examined. Histologic evaluation of a muscle biopsy specimen from 1 patient of Asidan, and neuropathologic evaluation of an autopsied brain from another patient of Asidan were also examined.
The mean age at onset was 53.1 years, with the most frequent symptoms of truncal ataxia (100% of patients), ataxic dysarthria (100%), limb ataxia (93%), and hyperreflexia (79%). Tongue fasciculation and subsequent atrophy were found in 71% of cases, particularly in those of long duration. Skeletal muscle fasciculation and atrophy of the limbs and trunk were found in 57% of cases. Most cases showed normal general cognitive function, but reduced frontal lobe functions, corresponding to frontal lobe atrophy on MRI. Lower motor involvement was confirmed by EMG and muscle biopsy. The neuropathologic study revealed significant cerebellar Purkinje cell degeneration with obvious loss of lower motor neurons. Although most patients did not show Parkinsonism, some showed decreases of DAT (dopamine transporter) image (DWEP=decreased DAT without evident Parkinsonism, Abe K 2016, Ohta et al., 2017).
Thus the novel ALS/SCA crossroad mutation Asidan (SCA36) showed unique clinical features, such as cerebellar ataxia, progressive motor neuron involvement, frontal cognitive decline, and a potential multi-system involvement.
