ALS2

MedlinePlus Genetics provides information about Amyotrophic lateral sclerosis

At least 20 ALS2 gene mutations have been found to cause infantile-onset ascending hereditary spastic paralysis. This disorder is characterized by progressive weakness and stiffness of muscles in the legs, arms, neck, and head that begins within the first 2 years of life. Mutations in the ALS2 gene alter the instructions for making alsin, often resulting in the production of an abnormally short alsin protein that is unstable and rapidly broken down. It is unclear exactly how ALS2 gene mutations cause infantile-onset ascending hereditary spastic paralysis. Research suggests that a lack of alsin and the subsequent loss of GTPase functions, such as endocytosis and the development of axons and dendrites, contribute to the progressive atrophy of motor neurons that is characteristic of this condition.

Researchers have identified three mutations in the ALS2 gene that cause juvenile primary lateral sclerosis, which is characterized by progressive weakness and stiffness of muscles in the arms, legs, and face that typically begins in childhood. Two of the mutations that cause this disorder delete nucleotides, and one mutation replaces one nucleotide with an incorrect nucleotide. These mutations alter the instructions for producing alsin. As a result, alsin is unstable and is broken down rapidly by the cell, or it is disabled and cannot function properly.

It is unclear how the loss of functional alsin protein causes juvenile primary lateral sclerosis. Loss of alsin may result in a disruption of the movement of molecules within cells or impair the development of axons and dendrites. Researchers suggest that motor neurons and their long axons may be particularly vulnerable to changes in cell development. As a result, motor neuron function declines and eventually these nerve cells die, leading to the signs and symptoms of juvenile primary lateral sclerosis.