High cognitive outcome in an adolescent with mut- methylmalonic acidemia
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Updated: Oct 2, 2026

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
Published on: December 16, 2021
L Varvogli1, G M Repetto, S E Waisbren
1Division of Genetics, Department of Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
Abstract:
Methylmalonic acidemia is an inborn error of metabolism known to be a cause of ketoacidosis and mental retardation. The less severe mut(-) form of the disorder, however, has been described with only mild to moderate cognitive deficits or, rarely, with normal neurodevelopment in asymptomatic cases. Nevertheless, there has been no detailed documentation of long-term neuropsychological function in the mut(-) form and relatively few IQ scores. We performed longitudinal developmental and neuropsychological assessments on a girl with symptomatic mut(-) methylmalonic acidemia whose biochemical abnormalities were in the moderately severe range and who had had recurrent episodes of ketoacidosis. At almost 12 years of age, her full scale IQ on the Wechsler Intelligence Scale, third edition, was 129 with very superior and superior scores on nonverbal and verbal skills, respectively. On the National Achievement Test she scored above the 99th percentile in the Basic Battery and is considered to be a gifted student. This outcome suggests that the spectrum of cognitive attainment in mut(-) methylmalonic acidemia is wide and that even a moderate degree of biochemical severity with ketoacidotic episodes may not result in cognitive deficit. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:192-195, 2000.
Insights
Methylmalonic acidemia (MMA) can present with varying cognitive outcomes. Even with moderate biochemical severity and ketoacidosis, some individuals with the mut(-) form of MMA may achieve gifted intellectual status.
Area of Science:
- Biochemistry
- Genetics
- Neurodevelopmental Disorders
Background:
- Methylmalonic acidemia (MMA) is an inherited metabolic disorder.
- The mut(-) form of MMA is typically associated with mild to moderate cognitive deficits.
Observation:
- A longitudinal study assessed a girl with symptomatic mut(-) MMA and recurrent ketoacidosis.
- Biochemical abnormalities were in the moderately severe range.
Findings:
- At nearly 12 years old, she achieved a full-scale IQ of 129.
- She scored above the 99th percentile on the National Achievement Test, indicating giftedness.
Implications:
- The cognitive spectrum in mut(-) MMA is broader than previously documented.
- Moderate biochemical severity and ketoacidotic episodes do not always lead to cognitive impairment.
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