MEGDEL syndrome ... (MEGDEL syndrome) - Gen SERAC1.
The MEGDEL syndrome is a hereditary disorder that affects multiple organ systems. Nomenclature comes from several features: 3-methylglutaconic aciduria (MEG), deafness (D: deafness), encephalopathy (E) and Leigh disease (L).
This disease can be diagnosed by the presence of abnormally high concentrations of 3-methylglutaconic aciduria and 3-methylglutaric acid. In childhood, affected individuals develop sensorineural hearing loss that gradually worsens over time. Another feature of MEGDEL syndrome is encephalopathy, leading to difficulty feeding, growth retardation and hypotonia. Affected newborns develop dystonia and spasticity, which worsens over time. Because these brain and muscle problems, affected newborns have psychomotor retardation. MEGDEL people with intellectual disabilities syndrome have and never learn to speak. Additional features include changes in the brain that are similar to those of Leigh, hypoglycemia, liver and lactic acidosis syndrome. The life expectancy of people affected is unknown. Due to the serious health problems associated with some affected individuals do not survive beyond infancy.
This process is due to mutations in the gene SERAC1, located on the long arm of chromosome 6 (6q25.3). This gene encodes a protein whose function is not completely understood. However, it is believed that SERAC1 protein is involved in the remodeling of phospholipids, particularly phosphatidylglycerol. Other phospholipid cardiolipin called consists phosphatidylglycerol. Cardiolipin is a component of the membrane surrounding the mitochondria, which convert energy from food in a way that cells can be used, and is important for the proper functioning of these structures. Probably SERAC1 protein is also involved in the movement of cholesterol within cells.
They have identified at least 16 mutations in the gene responsible for MEGDEL SERAC1 syndrome. These mutations reduce the amount of encoded or result encoding a protein with little or no protein function. As a result, phosphatidylglycerol remodeling deteriorates, which probably it alters the composition of cardiolipin. It is believed that altered mitochondrial function affects cardiolipin, which reduces the production of cellular energy and leads to neurological and hearing problems characteristic of MEGDEL syndrome. It is unclear how mutations in the gene SERAC1 lead to abnormal release of 3-methylglutaconic in urine.
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 MEGDEL syndrome by complete PCR amplification of the gene exons SERAC1, 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).