EAST syndrome
| EAST syndrome | |
|---|---|
| Synonym | SeSAME syndrome |
| Pronunciation | |
| Classification and external resources | |
| OMIM | 612780 |
| MeSH | C557674 |
| Orphanet | 199343 |
EAST syndrome is a syndrome consisting of epilepsy, ataxia (a movement disorder), sensorineural deafness (deafness because of problems with the hearing nerve) and salt-wasting renal tubulopathy (salt loss caused by kidney problems). The tubulopathy (renal tubule abnormalities) in this condition predispose to hypokalemic (low potassium) metabolic alkalosis with normal blood pressure. Hypomagnesemia (low blood levels of magnesium) may also be present.
EAST syndrome is also called SeSAME syndrome, as a syndrome of seizures, sensorineural deafness, ataxia, intellectual disability (mental retardation), and electrolyte imbalances. It is an autosomal recessive genetic disorder caused by mutations in the KCNJ10 gene, as discovered by Bockenhauer and co-workers. The KCNJ10 gene encodes the K+ channel Kir.4 (allowing K+ to flow into a cell rather than out) and is present in the brain, ear, and kidney.
Many mutations that are found within EAST syndrome lead to a change in pH sensitivity and a modification in the IC50 value to the alkaline range, which is a higher pH reading. A specific KCNJ10 mutation, R65P, is affected by this shift. Its activity is greatly decreased when exposed to the intracellular pH. This causes more H+ sensitivity within humans, which means that the pH level is then shifted into the basic range. There are still many other mutations such as R175Q, T164I, and R297C that also cause changes in the pH sensitivity. These mutations also have decreased sensitivity when they are exposed to physiological intracellular pH.
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