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

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 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)
JournalPediatrics
Volume129
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Phenotype
Hyperammonemia
Basal Ganglia
Age of Onset
Cognition
Epilepsy
Seizures
Methylmalonic acidemia
Newborn Infant
Mutation
Wounds and Injuries
Onset
Testing
Processing Speed
Impairment

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Arts and Humanities (miscellaneous)

Cite this

O'Shea, C. J., Sloan, J. L., Wiggs, E. A., Pao, M., Gropman, A., Baker, E. H., ... Snow, J. (2012). Neurocognitive phenotype of isolated methylmalonic acidemia. Pediatrics, 129(6). https://doi.org/10.1542/peds.2011-1715

Neurocognitive phenotype of isolated methylmalonic acidemia. / O'Shea, Colin J.; Sloan, Jennifer L.; Wiggs, Edythe A.; Pao, Maryland; Gropman, Andrea; Baker, Eva H.; Manoli, Irini; Venditti, Charles P.; Snow, Joseph.

In: Pediatrics, Vol. 129, No. 6, 06.2012.

Research output: Contribution to journalArticle

O'Shea, CJ, Sloan, JL, Wiggs, EA, Pao, M, Gropman, A, Baker, EH, Manoli, I, Venditti, CP & Snow, J 2012, 'Neurocognitive phenotype of isolated methylmalonic acidemia', Pediatrics, vol. 129, no. 6. https://doi.org/10.1542/peds.2011-1715
O'Shea CJ, Sloan JL, Wiggs EA, Pao M, Gropman A, Baker EH et al. Neurocognitive phenotype of isolated methylmalonic acidemia. Pediatrics. 2012 Jun;129(6). https://doi.org/10.1542/peds.2011-1715
O'Shea, Colin J. ; Sloan, Jennifer L. ; Wiggs, Edythe A. ; Pao, Maryland ; Gropman, Andrea ; Baker, Eva H. ; Manoli, Irini ; Venditti, Charles P. ; Snow, Joseph. / Neurocognitive phenotype of isolated methylmalonic acidemia. In: Pediatrics. 2012 ; Vol. 129, No. 6.
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N2 - 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.

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