title: Dystonia and deafness due to SUCLA2 defect; Clinical course and biochemical markers in 16 children.
abstract: Patients with SUCLA2 gene defects characteristically develop the trias of early hypotonia, progressive dystonia and sensori-neural deafness. We describe the clinical course and biochemical phenotype in 16 children from the Faroe Islands with a homozygous SUCLA2 splice site mutation. Elevated urinary 3-hydroxyisovaleric acid is a novel biochemical feature in patients. Progressive hearing loss, in combination with a characteristic metabolite profile (increased lactate, methylmalonic acid, C4-dicarboxylic carnitine, 3-hydroxyisovaleric acid) should lead the clinician to the correct diagnosis even in patients with only intermittent lactic acidemia. Direct SUCLA2 sequence analysis is suggested instead of an invasive muscle biopsy to obtain the diagnosis. Nutritional intervention may be considered in SUCLA2 patients.
authors: Departments of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, The Netherlands. e.morava@cukz.umcn.nl
authors: Eva
authors: E
authors: Morava
authors: Ulrike
authors: U
authors: Steuerwald
authors: Rosalba
authors: R
authors: Carrozzo
authors: Leo A J
authors: LA
authors: Kluijtmans
authors: Frodi
authors: F
authors: Joensen
authors: René
authors: R
authors: Santer
authors: Carlo
authors: C
authors: Dionisi-Vici
authors: Ron A
authors: RA
authors: Wevers
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D004421:Dystonia / Q000175:diagnosis* / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007223:Infant; D007773:Lactates / Q000097:blood; D008297:Male; D053858:Metabolic Networks and Pathways; D008764:Methylmalonic Acid / Q000097:blood; D008954:Models, Biological; D013389:Succinate-CoA Ligases / Q000172:deficiency* / Q000235:genetics; D014631:Valerates / Q000652:urine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007773:Lactates; D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D008764:Methylmalonic Acid; D013389:Succinate-CoA Ligases; C518788:SUCLA2 protein, human