Hereditary spastic paralysis ascending infantile onset (Infantile-onset ascending hereditary spastic paralysis) - Gen ALS2
The upward spastic paralysis of childhood - onset hereditariaes an alteration characterized by spasticity and paraplegia due to atrophy of motor neurons. Hereditary spastic paraplegia the are divided into two types: pure and complicated. Pure types affect only the lower limbs, while complicated types affect additional areas of the nervous system, altering the upper extremities and other areas of the body. Spastic paralysis ascending hereditary infantile onset begins as a hereditary spastic paraplegia pure, with the manifestation of spasticity and weakness only in the legs, but as the disease progresses, it affects the muscles of the arms, neck and head and the features of the disease are more characteristic of complicated type.
Usually the initial symptoms of the disease manifest in the first two years of life. These symptoms include hyperreflexia and frequent muscle spasms in the legs. As the disease progresses, affected children develop stiffness and weakness in the legs and arms. Over time, muscle weakness and stiffness in the body rise from the legs to the head. In late childhood or early adolescence, the disease affects the muscles of the arm and hand. The muscles of the neck and head usually weaken during adolescence. Additional symptoms include slow eye movements and difficulty with speech and swallowing.
A disease called juvenile primary lateral sclerosis shares many of the characteristics of hereditary spastic paralysis ascending infantile onset. Both processes have the same genetic cause significantly affect movement in childhood; However, the pattern of nerve degeneration is different. Because of their similarities, these diseases are sometimes considered the same entity.
This process is due to mutations in the gene ALS2 (ALS2, Alsin Rho guanine nucleotide exchange factor), located on the long arm of chromosome 2 (2q33.1). This gene encodes the protein alsin. Alsina occurs in a wide range of tissues, with higher concentrations in the brain. This protein is particularly abundant in motor neurons. Although alsina seems to have many functions, only they are known some of them. This active protein GTPases that convert GTP to GDP. GTPases play an important role in cell division, cell differentiation and apoptosis. In addition, it is likely that alsina play a role in endocytosis and the development of axons and dendrites.
They have identified at least 20 genetic mutations in individuals with ALS2 ascending hereditary spastic paralysis infantile onset. This mutation changes or eliminate one or more nucleotides, which changes the encoding alsin. As a result, the shoring is unstable and rapidly decomposes. Although it is unclear how the loss of alsina proteins leads to illness, it is likely to alter the movement of essential molecules inside the cells or alter the development of axons and dendrites. It is believed that the long axons are particularly sensitive to developmental abnormality. Alsina functional loss leads to decreased function of motor neurons, which in turn causes the death of these nerve cells, leading to the signs and symptoms of the disease.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with hereditary spastic paralysis infantile onset upwards through the complete PCR amplification of exons ALS2 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).