In Japan researchers at the Juntendo University have discovered that when ECHS1 enzyme variations of mitochondrial enoyl-CoA hydratase short chain 1 (ECHS 1) do not function properly, they cause mitochondrial disease. This is believed to be the most common cause of mitochondrial disease in Japan. ECHS1 is an enzyme involved in the metabolism of branched-chain amino acids and fatty acids
Mitochondria produce energy in most of our cells by combining oxygen with fats and sugars from our food. When they are defective the cells are deprived of energy. The oxygen that is unused builds up together with fuel molecules in the cells and causes damage.
The symptoms of mitochondrial disorder vary in accordance with the type and severity of mitochondria that are defective and their location in the body. Symptoms range in severity and some may be fatal.
It is therefore assumed that profiling ECHS1 variants of uncertain significance (VUS), the most common cause of mitochondrial disease will aid in the diagnosis of mitochondrial disorder during its early stages. In this regard, scientists have developed a high-throughput assay combined with a biological analysis approach using datasets with “omes” such as proteome and genome. The combination rapidly identifies and validates ECHS1VUS genetic variants that malfunction as well as other mitochondrial disease genes.
Yet it is not uncommon for a close relative in a family to be the first person (known as a proband) to bring his or her concern about the disorder to the attention of healthcare professionals.
About Valine
Mutations that are inherited in ECHS1 may result in ECHS1 deficiency and disruption of valine and accumulation of valine intermediates such as diaminopimelic acid, an essential amino acid. Valine facilitates a smooth nervous system and cognitive functioning.
In addition, these mutant enzymes cause lesions in the brain and delays in a child’s psychomotor development. Blood lactate levels that are impacted by the liver may become elevated.
Many disease-causing mutations have been found throughout the ECHS1 gene. ECHS1 VUS has increased which has an impact on genetic diagnosis.
CRISPR Cas9
Assays that combine genomic sequencing and CRISPR Cas9 are now routinely used in cancer searching for ECHS1 VUS.
Recently a research team from the IDR Center of Japan’s University of Juntendo developed an assay system that validates ECHS1 variants.
The team’s findings appeared in the Medical Genetics Journal in April of this year. Only 40% of cases have been diagnosed with 30% having VUS, so researchers cannot predict the cause of the disease.
Team Leader Professor Okazaki was pleased to announce that although the system is complex, the assay was quick to pinpoint the circumstances surrounding the loss of ECHS1 function.
The team was elated that their “omics” analysis caught several cases that the assay had not detected. The researchers felt confident that they can improve patients’ lives.
