Neurocognitive phenotype of isolated methylmalonic acidemia

Colin J. O'Shea, Jennifer L. Sloan, Edythe A. Wiggs, Maryland Pao, Andrea Gropman, Eva H. Baker, Irini Manoli, Charles P. Venditti, Joseph Snow

Research output: Contribution to journalArticle


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 plusmn; SD full-scale IQ (FSIQ) of 71.1 ± 14.75. Late-onset mut patients (n = 6) had a mean FSIQ of 88.5 plusmn; 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 plusmn; 10.95, 96.6 plusmn; 10.92, and 106.7 plusmn; 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.

Original languageEnglish (US)
Pages (from-to)e1541-e1551
Issue number6
StatePublished - Jun 2012


  • Basal ganglia
  • Cognition
  • FSIQ
  • Hyperammonemia
  • IQ
  • MMA
  • Methylmalonic acidemia
  • Neuropsychology

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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