TY - JOUR
T1 - Neurocognitive phenotype of isolated methylmalonic acidemia
AU - O'Shea, Colin J.
AU - Sloan, Jennifer L.
AU - Wiggs, Edythe A.
AU - Pao, Maryland
AU - Gropman, Andrea
AU - Baker, Eva H.
AU - Manoli, Irini
AU - Venditti, Charles P.
AU - Snow, Joseph
PY - 2012/6
Y1 - 2012/6
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.
AB - 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.
KW - Basal ganglia
KW - Cognition
KW - FSIQ
KW - Hyperammonemia
KW - IQ
KW - MMA
KW - Methylmalonic acidemia
KW - Neuropsychology
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U2 - 10.1542/peds.2011-1715
DO - 10.1542/peds.2011-1715
M3 - Article
C2 - 22614770
AN - SCOPUS:84861917594
SN - 0031-4005
VL - 129
SP - e1541-e1551
JO - Pediatrics
JF - Pediatrics
IS - 6
ER -