High cognitive outcome in an adolescent with mut? methylmalonic acidemia

Varvogli, Liza; Repetto, Gabriela M.; Waisbren, Susan E.; Levy, Harvey L.

doi:10.1002/(sici)1096-8628(20000403)96:2<192::aid-ajmg14>3.0.co;2-j

Cited by 10 publications

(5 citation statements)

References 16 publications

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“…It is characterized by deficient activity of methylmalonyl-CoA mutase (MCM), the vitamin B12-dependent enzyme responsible for converting methylmalonyl-CoA to succinyl-CoA (1)(2)(3)(4). MMAemia is caused by complete (mut0) or partial (mut-) deficiency of MCM or by defects in the synthesis of adenosylcobalamin (cblA, cblB), which is the cofactor for MCM (2).…”

Section: Introductionsupporting

confidence: 83%

“…The cardinal metabolic expression of MMAemia is an accumulation of methylmalonic acid (MMA), which is most readily detected in urine. The clinical phenotype includes ketoacidosis, developmental delay with subsequent mental retardation, and in the most severe cases, infant death (1)(2)(3)(4). The key distinguishing feature of the response to therapy and prognosis is the in vivo response to parenteral vitamin B12 supplements for several days (4).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of Living Donor Liver Transplantation for Patients With Methylmalonic Acidemia

Morioka¹,

Kasahara²,

Horikawa³

et al. 2007

American Journal of Transplantation

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Application of liver transplantation to methylmalonic acidemia (MMAemia) is controversial because MMAemia is caused by a systemic defect of methylmalonyl-CoA mutase. The clinical courses of seven pediatric patients with MMAemia undergoing living donor liver transplantation (LDLT) were reviewed. Serum and urinary methylmalonic acid (MMA) levels were found to be significantly decreased after LDLT, whereas serum and urinary MMA levels did not return to normal in any patient. One patient died of sepsis 44 days after LDLT. The other six patients are currently doing well. All patients had preoperative history of acute metabolic decompensation and/or metabolic stroke. However, no episode of acute metabolic decompensation or metabolic stroke was observed postoperatively in any surviving patients. In the preoperative period, all patients showed lethargy and cognitive deficit, both of which were eradicated after LDLT in all surviving patients. Preoperatively, all patients were subjected to dietary protein intake restriction and tube feeding, and were administered several metabolism-correcting medications. The metabolism-correcting medications being administered remained mostly unchanged after LDLT, whereas protein restriction was liberalized and tube feeding became unnecessary in all surviving patients. In addition, physical and neurodevelopmental growth delay remained in all surviving patients during the observation period, which ranged from 4 to 21 months with a median of 10.5 months.

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Section: Introductionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Efficacy of Living Donor Liver Transplantation for Patients With Methylmalonic Acidemia

Morioka¹,

Kasahara²,

Horikawa³

et al. 2007

American Journal of Transplantation

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“…This demonstrates that current biomedical treatment of cblC does not prevent cognitive impairment, even if started at an early age in screened, asymptomatic newborns, and indicates the potential utility of timely neuropsychological assessment. The clinical heterogeneity revealed here extends the previously reported findings (Beauchamp et al 2009;Longo et al 2005;Varvogli et al 2000;Weisfeld-Adams et al 2013). Clearly, cblC does not cause a consistent pattern of cognitive functioning.…”

Section: Neuropsychological Assessment In Cblc Patientssupporting

confidence: 88%

A Highly Diverse Portrait: Heterogeneity of Neuropsychological Profiles in cblC Defect

et al. 2015

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Cobalamin C is a rare inborn disorder of metabolism that results in multisystemic abnormalities, including progressive visual deficits. Although the cellular pathophysiology of cblC is a field of active study, little attention has been dedicated to documenting the cognitive consequences of the defect. The neuropsychological assessment of nine individuals aged between 23 months and 24 years was conducted to establish cognitive profiles. Results reveal a marked heterogeneity, with intellectual functioning ranging from extremely low to average, and cognitive difficulties (e.g., attention) evidenced even in those who are not intellectually disabled. Central nervous system abnormalities and multisystem disease are likely to be major contributing factors to the observed cognitive impairments, with the presence of visual deficits constituting an additional impediment to normal cognitive development. This study underscores the importance of conduct ing in-depth neuropsychological assessments in individuals with cblC, the results of which may be particularly helpful for clinical management, guidance toward rehabilitation services, and educational/vocational planning.

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“…5 The disorder is difficult to manage and has a highly variable outcome. [6][7][8][9][10][11][12] Treatment options involve injections of vitamin B 12 in responsive patients 13 ; strict adherence to a low-protein diet; carnitine supplementation; and solid organ transplantation. 14 Neurocognitive and neurologic deficits have been recognized to occur in patients with MMA, 6,8,11 including global developmental delay and hyperkinetic movement disorders secondary to basal ganglia injury.…”

Section: Discussionmentioning

confidence: 99%

“…This observation bolsters a previous case report 12 demonstrating exceptional abilities in a patient with biochemically severe MMA. Although numerous cell studies have claimed that methylmalonic acid itself is neurotoxic, 37,38 the patient data indicate that sequelae of neurodegeneration, if present, may exhibit a very slow rate of progression and/or manifest only in a select group of nuclei that control processing speed.…”

Section: Discussionmentioning

confidence: 99%

Neurocognitive Phenotype of Isolated Methylmalonic Acidemia

2012

PEDIATRICS

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WHAT'S KNOWN ON THIS SUBJECT: Isolated methylmalonic acidemia, one of the most common inborn errors of organic acid metabolism, is known to be associated with variably impaired intellectual functioning and severe biochemical and clinical abnormalities. However, the neurocognitive outcomes have yet to be fully described. WHAT THIS STUDY ADDS:This research defines the neurocognitive phenotype of isolated methylmalonic acidemia and identifies processing speed as a specific impairment. Clinical, biochemical, and molecular genetic covariates were explored. A history of hyperammonemia at diagnosis was found to correlate with poorer cognitive outcomes. 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 6 SD full-scale IQ (FSIQ) of 71.1 6 14.75. Late-onset mut patients (n = 6) had a mean FSIQ of 88.5 6 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 6 10.95, 96.6 6 10.92, and 106.7 6 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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High cognitive outcome in an adolescent with mut? methylmalonic acidemia

Cited by 10 publications

References 16 publications

Efficacy of Living Donor Liver Transplantation for Patients With Methylmalonic Acidemia

Efficacy of Living Donor Liver Transplantation for Patients With Methylmalonic Acidemia

A Highly Diverse Portrait: Heterogeneity of Neuropsychological Profiles in cblC Defect

Neurocognitive Phenotype of Isolated Methylmalonic Acidemia

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