title: Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.
abstract: Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland. d.abramczuk@czd.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.affiliation: Department of Child and Adolescent Neurology, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Mierzewska
authors.affiliation: Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Bekiesińska-Figatowska
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Ciara
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Trubicka
authors.affiliation: Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Pronicki
authors.affiliation: Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rokicki
authors.affiliation: Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.affiliation: Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.|Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pronicka
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D002675:Child, Preschool; D004421:Dystonia / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D035781:Siblings; D012871:Skin Diseases / Q000150:complications / Q000235:genetics*; D020955:Striatonigral Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics
chemical_list: D016601:RNA-Binding Proteins; D000243:Adenosine Deaminase
keywords:  ADAR gene;  LS differentiation;  whole exome sequencing; bilateral striatal necrosis