Two Turkish siblings with MEGDEL syndrome due to novel SERAC1 gene mutation

Association of 3-methylglutaconic aciduria with impaired oxidative phosphorylation, deafness, encephalopathy, leigh-like lesions on brain imaging, progressive spasticity and dystonia defined as a distinct entity under the name of MEGDEL syndrome. It is an autosomal recessive disorder due to mutation in the serine active site-containing protein 1 (SERAC1). SERAC1 is localized at the interface between the mitochondria and the endoplasmic reticulum in the mitochondria-associated membrane fraction that is essential for phospholipid exchange. It was identified as a key player in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. Here we report two new Turkish sibling patients affected with MEGDEL syndrome due to SERAC1 gene mutation. The patients were presented with 3-methylglutaconic acid and 3-methylglutaric aciduria, microcephaly, growth retardation, dysmorphic features, severe sensorineural deafness, progressive spasticity, dystonia, seizures, basal ganglia involvement. Metabolic acidosis, mild hyperammonemia and lactic acidemia were accompanied with clinical findings in newborn period.