Progressive muscular atrophy variant of familial amyotrophic lateral sclerosis (PMA/ALS)

Twelve cases of adult-onset progressive muscular atrophy variant of amyotro phic lateral sclerosis (PMA/ALS) were studied in a small rural population o f 1500 in the Republic of Belarus (former Soviet Union). The patients were members of three apparently related kindreds, each showing autosomal domina nt pattern of disease inheritance. The average age at clinical onset ranged from 26 to 57 years (mean, 40 years). Each patient suffered from skeletal muscle weakness and wasting, starting in the limbs and spreading to the tru nk and neck, with very limited bulbar and no upper motor neuron involvement . Death from respiratory failure occurred from 13 to 48 months (mean, 28 mo nths) after first symptoms. Dramatically decreased number of spinal motor n eurons was the most characteristic neuropathologic feature in two autopsied cases. Most of the remaining degenerating neurons contained intracytoplasm ic hyaline inclusion bodies. A D101N mutation in exon 4 of the SOD1 gene wa s identified in a PMA/ALS patient and in one of her three unaffected childr en. Our data support the view that some subtypes of familial ALS associated with SOD1 mutations may present as PMA. Diagnostic criteria of ALS should be accordingly modified to include the PMA variant of familial ALS. (C) 200 0 Published by Elsevier Science B.V.