title: Clinical and neurocognitive outcome in symptomatic isovaleric acidemia.
abstract: BACKGROUND
  Despite its first description over 40 years ago, knowledge of the clinical course of isovaleric acidemia (IVA), a disorder predisposing to severe acidotic episodes during catabolic stress, is still anecdotal. We aimed to investigate the phenotypic presentation and factors determining the neurological and neurocognitive outcomes of patients diagnosed with IVA following clinical manifestation.
  
  
  METHODS
  Retrospective data on 21 children and adults with symptomatic IVA diagnosed from 1976 to 1999 were analyzed for outcome determinants including age at diagnosis and number of catabolic episodes. Sixteen of 21 patients were evaluated cross-sectionally focusing on the neurological and neurocognitive status. Additionally, 155 cases of patients with IVA published in the international literature were reviewed and analyzed for outcome parameters including mortality.
  
  
  RESULTS
  57% of study patients (12/21) were diagnosed within the first weeks of life and 43% (9/21) in childhood. An acute metabolic attack was the main cause of diagnostic work-up. 44% of investigated study patients (7/16) showed mild motor dysfunction and only 19% (3/16) had cognitive deficits. No other organ complications were found. The patients' intelligence quotient was not related to the number of catabolic episodes but was inversely related to age at diagnosis. In published cases, mortality was high (33%) if associated with neonatal diagnosis, following manifestation at an average age of 7 days.
  
  
  CONCLUSIONS
  Within the group of "classical" organic acidurias, IVA appears to be exceptional considering its milder neuropathologic implications. The potential to avoid neonatal mortality and to improve neurologic and cognitive outcome under early treatment reinforces IVA to be qualified for newborn screening.
authors.affiliation: Center for Pediatrics and Adolescent Medicine, Albert-Ludwigs-Universität Freiburg, Germany.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Grünert
authors.forename: Udo
authors.initials: U
authors.lastname: Wendel
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.forename: Michael
authors.initials: M
authors.lastname: Leichsenring
authors.forename: K Otfried
authors.initials: KO
authors.lastname: Schwab
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.forename: Willy
authors.initials: W
authors.lastname: Lehnert
authors.forename: Regina
authors.initials: R
authors.lastname: Ensenauer
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability; D050769:Isovaleryl-CoA Dehydrogenase / Q000172:deficiency; D008297:Male; D011596:Psychomotor Disorders / Q000150:complications*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D050769:Isovaleryl-CoA Dehydrogenase