Alternating Hemiplegia of Childhood (Alternating hemiplegia of childhood) - Genes ATP1A2 or ATP1A3
Alternating Hemiplegia of Childhood is a neurological disorder characterized by recurrent episodes of temporary paralysis that often affect one side of the body. During some episodes, alternating paralysis from one side of the body to another, or affects both sides at the same time. These episodes begin in infancy or early childhood, usually before 18 months of age and paralysis can last from minutes to days. In addition to paralysis, those affected may suffer sudden attacks of uncontrollable muscle activity that can cause choreoathetosis, dystonia, nystagmus , and dyspnea. Other signs and symptoms include additional flushing or pale skin.
Episodes of hemiplegia or uncontrolled movements can be triggered by certain situations such as stress, severe tiredness, cold temperatures, or bath, but not always the trigger is known. A characteristic feature of this disease is that all symptoms disappear when the affected person is sleeping, but may recur shortly after waking. The number and duration of episodes initially worsens throughout childhood, but begin to decrease over time. Uncontrollable muscle movements may disappear entirely but episodes of hemiplegia can occur throughout life. Alternating Hemiplegia of Childhood also causes cognitive problems ranging from mild to severe. Almost all affected individuals have some level of developmental delay and intellectual disability. Normally, their cognitive performance declines with time.
This disease is mainly due to mutations in the gene ATP1A3 (ATPase Na + / K + alpha subunit Transporting 3), located on the long arm of chromosome 19 (19q13.31). Rarely, a mutation in the gene ATP1A2 (ATPase Na + / K + alpha subunit Transporting 2), located on the long arm of chromosome 1 (1q23.2), is associated with the disease. The ATP1A2 and ATP1A3 genes encoding the alpha subunit 2 and alpha 3 subunit, respectively, of the Na + / K + ATPase protein. The two versions of the complex are located in different parts of the brain. Both versions play a critical role in the normal function of neurons. Na + / K + -ATPase transports ions inside and outside of neurons, which is an essential part of the signaling process that controls muscle movement.
They have identified at least 25 mutations in the ATP1A3 gene and a mutation in the gene ATP1A2 in people with childhood hemiplegia alternating. Most genetic mutation changes ATP1A3 amino acids in the alpha-3 subunit of Na + / K + ATPase. These genetic changes appear to affect the ability of ion transport, although it is unclear how mutations lead to the specific characteristics of the disease. Meanwhile, ATP1A2 gene mutation known amino acid threonine replaced by the amino acid asparagine at position 378 of the alpha-2 subunit protein in Na + / K + ATPase (Thr378Asn or T378N). Although it is unclear how the mutation leads to the specific characteristics of the disease, this genetic change is likely impairs the ability of the protein to transport ions.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. Most cases of Alternating Hemiplegia of childhood are due to new mutations in the gene and occur in people with no history of disease in your family. For unknown reasons, the signs and symptoms are generally milder when the disease is present in multiple family members when one individual is affected.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Alternating Hemiplegia of Childhood, by complete PCR amplification of the exons of ATP1A2 and ATP1A3, respectively, and subsequent sequencing genes.
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).