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

• Published in: Journal of the neurological sciences 2000-08, Vol.177 (2), p.124-130
• Main Authors: Cervenakova, Larisa, Protas, Iosif I, Hirano, Asao, Votiakov, Veniamin I, Nedzved, Mikhail K, Kolomiets, Natalia D, Taller, Inna, Park, Kye-Yoon, Sambuughin, Nyamkhishig, Gajdusek, D.Carleton, Brown, Paul, Goldfarb, Lev G
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - pathology; Belarus; Biological and medical sciences; D101N mutation; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Familial amyotrophic lateral sclerosis; Female; Humans; Male; Medical sciences; Middle Aged; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - pathology; Neurology; Pedigree; Phenotype; Republic of Belarus; Rural Population; SOD1 gene; Spinal Cord - pathology; Superoxide Dismutase - genetics
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(00)00350-6

Twelve cases of adult-onset progressive muscular atrophy variant of amyotrophic lateral sclerosis (PMA/ALS) were studied in a small rural population of 1500 in the Republic of Belarus (former Soviet Union). The patients were members of three apparently related kindreds, each showing autosomal dominant 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 trunk and neck, with very limited bulbar and no upper motor neuron involvement. Death from respiratory failure occurred from 13 to 48 months (mean, 28 months) after first symptoms. Dramatically decreased number of spinal motor neurons was the most characteristic neuropathologic feature in two autopsied cases. Most of the remaining degenerating neurons contained intracytoplasmic hyaline inclusion bodies. A D101N mutation in exon 4 of the SOD1 gene was identified in a PMA/ALS patient and in one of her three unaffected children. 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.