Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. It is characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence in Western countries averages around 1/50,000 per year and prevalence averages around 1/20,000. Onset occurs early, and delayed walking is observed in patients. Speech may get slurred later. Generalized muscle weakness is progressive, leading to dyspnea and excessive fatigue with mild exertion even during the first decades. Disease progression leads to shortness of breath and excessive tiredness which may cause death. Juvenile ALS has many of the clinical features of adult-onset ALS except for its apparent autosomal recessive mode of inheritance and earlier onset.
The diagnosis of ALS is based on clinical history, examination, and electromyography testing might contributes to the diagnostic accuracy. ALS is an incurable fatal disease, with median survival of 3-5 years. Treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. Supportive care is best provided by health care professionals to keep the patients as mobile and comfortable as possible.
Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of juvenile ALS and has been mapped to human chromosome 2q33. The ALS2 gene is expressed in many tissues and cells, and encodes a protein particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles including neurons.
Ben Hamida et al. (1990) described 43 patients from 17 Tunisian families with hereditary motor system diseases. This included a large inbred kinship, patients in which were characterized by a loss of upper motor neurons and spasticity of limbs and facial muscles, accompanied distal amyotrophy of hands and feet. This same family was later studied by Hentati et al. (1994), who used linkage analysis to localize the ALS2 gene in the family to an 8 cM region on 2q33-35. Later, Hadano et al. (2001) undertook a study to detect mutations in this family by exome screening of all putative genes in the region. They identified a single nucleotide deletion in exon 3 (c.261delA) of the ALS2CR6 gene. All affected patients were homozygous for the mutation, while all predicted carriers were heterozygous. The mutation was not found in 533 unrelated controls.