Brain, Vol. 119, No. 4, 1153-1172, 1996
© 1996 Guarantors of Brain
research-article |
Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation
A clinical and genealogical study of 36 patients
1Departments of Neurology, Umeå University Hospital Umeå, Sweden 2Departments of Clinical Chemistry, Umeå University Hospital Umeå, Sweden 3Departments of Clinical Neurophysiology, Umeå University Hospital Umeå, Sweden 4Department of Neurology, Kemi Hospital Kemi 5Department of Neurology, Lapin Keskussairaala Rovaniemi 6Department of Neurology, Kainuun Keskussairaala Kajaani 7Kauniala Hospital for injured Veterans Kauniainen 8Department of Neurology Mikkeli Hospital Mikkeli 9Department of Neurology, Hyvinkään Hospital Hyvinkää 10Department of Neurology, Vaasa Hospital Vaasa, Finland
Correspondence to:
Correspondence to: Dr Peter M. Andersen, Department of Neurology, Umeå University Hospital, S-901 85 Umeå, Sweden
We describe 36 patients (six were apparently sporadic cases and 30 were cases from nine families) with amyotrophic lateral sclerosis (ALS) characterized by a distinct phenotype associated with homozygosity for an Asp90Ala mutation in the CuZn-superoxide dismutase gene. The presenting motor manifestation in all patients was paresis in the legs, with slow progression to the upper extremities and finally to the bulbar muscles. The age of ALS onset varied from 20 to 94 years, with a mean of 44 years. Mean survival time was 13 years for the 11 deceased patients. However, this is probably biased and untypical (low) when compared with the disease duration in the surviving patients, and when considering other medical complications in the deceased patients. The rate of progression was highly variable, even within families. All patients showed signs of involvement of both upper and lower motor neurons. Other neurological features included painful muscle spasms and paraesthesiae in the lower extremities. Two-thirds of patients experienced difficulty with micturition. Electrophysiological studies confirmed the slow progression and spatial distribution of clinical symptoms in the peripheral motor system. Furthermore, EMG potentials evoked by transcranial magnetic stimulation (MEP) were compared with those evoked by cervical or lumbosacral electrical stimulation and often revealed marked slowing of transmission in central motor pathways. In Sweden and Finland ALS patients homozygous for the Asp90Ala mutation constitute a phenotypically characteristic subset of motor neuron disease.
Asp90Ala CuZn-SOD mulation; autosomal recessive adult-onset amyotrophic lateral sclerosis; motor neuron disease
Received December 22, 1995. Revised February 26, 1996. Accepted April 1, 1996.
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