title: Neurocognitive phenotype of isolated methylmalonic acidemia.
abstract: OBJECTIVE
  Methylmalonic acidemia (MMA) is a metabolic disorder with a poorly defined long-term neurocognitive phenotype. We studied the neuropsychological outcomes of patients and examined clinical covariates that influenced cognition.
  
  
  METHODS
  A diverse cohort with mut, cblA, or cblB subtypes of isolated MMA (N = 43), ages 2 to 32 years, were evaluated at a single center over a 6-year period. The influence of clinical, laboratory, and metabolic parameters on neuropsychological testing results was determined.
  
  
  RESULTS
  Early-onset mut patients (n = 21) manifested the most severe neurocognitive impairments, with a mean ± SD full-scale IQ (FSIQ) of 71.1 ± 14.75. Late-onset mut patients (n = 6) had a mean FSIQ of 88.5 ± 27.62. cblA (n = 7), cblB (n = 6), and mut patients diagnosed prenatally or by newborn screening (n = 3) obtained mean FSIQs in the average range (100.7 ± 10.95, 96.6 ± 10.92, and 106.7 ± 6.66, respectively). Hyperammonemia at diagnosis and the presence of a seizure disorder were associated with a lower FSIQ (P = .001 and P = .041, respectively), but other clinical variables, including basal ganglia injury and mutation status, did not. FSIQ remained stable over longitudinal testing (n = 10). Decreased scores on processing speed, compared with all other intellectual domains, emerged as a specific neurocognitive manifestation.
  
  
  CONCLUSIONS
  The neurocognitive outcomes seen in isolated MMA are highly variable. An earlier age of disease onset, the presence of hyperammonemia at diagnosis, and a history of seizures were associated with more severe impairment. In all patient subtypes, selective deficits in processing speed were present.
authors.affiliation: National Institute of Mental Health, National Institutes of Health, Building 49 Room 4A18 Bethesda, MD 20892-4472, USA.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: O'Shea
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sloan
authors.forename: Edythe A
authors.initials: EA
authors.lastname: Wiggs
authors.forename: Maryland
authors.initials: M
authors.lastname: Pao
authors.forename: Andrea
authors.initials: A
authors.lastname: Gropman
authors.forename: Eva H
authors.initials: EH
authors.lastname: Baker
authors.forename: Irini
authors.initials: I
authors.lastname: Manoli
authors.forename: Charles P
authors.initials: CP
authors.lastname: Venditti
authors.forename: Joseph
authors.initials: J
authors.lastname: Snow
mesh_terms: D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology*; D015331:Cohort Studies; D004827:Epilepsy / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D010641:Phenotype; D055815:Young Adult