title: Two Turkish siblings with MEGDEL syndrome due to novel SERAC1 gene mutation.
abstract: 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.
authors.affiliation: Division of Pediatric Metabolism, Department of Pediatrics Faculty of Medicine, Hacettepe University, Ankara, Turkey. unalozlem@gmail.com.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Ünal
authors.forename: R Köksal
authors.initials: RK
authors.lastname: Özgül
authors.forename: Didem
authors.initials: D
authors.lastname: Yücel
authors.forename: Dilek
authors.initials: D
authors.lastname: Yalnızoğlu
authors.forename: Ayşegül
authors.initials: A
authors.lastname: Tokatlı
authors.forename: H Serap
authors.initials: HS
authors.lastname: Sivri
authors.forename: Burcu
authors.initials: B
authors.lastname: Hişmi
authors.forename: Turgay
authors.initials: T
authors.lastname: Coşkun
authors.forename: Ali
authors.initials: A
authors.lastname: Dursun
mesh_terms: D001927:Brain Diseases / Q000235:genetics; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D003638:Deafness / Q000235:genetics; D004421:Dystonia / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007888:Leigh Disease / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics; D009128:Muscle Spasticity / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D035781:Siblings; D013577:Syndrome; D014421:Turkey
chemical_list: D002265:Carboxylic Ester Hydrolases; C576043:SERAC1 protein, human