Methylmalonic aciduria is an inborn error of metabolism that results in accumulation of methylmalonic acid in the blood and urine. This could be secondary to complete or partial deficiency of methylmalonyl-CoA mutase. The most common form presents in infancy with lethargy, hypotonia, encephalopathy, and vomiting. Adult onset of disease can present with variable symptoms, of which movement disorders are apparent in up to 45% of cases.

A 37-year-old female with no significant medical history presented for throbbing holocephalic headache. MRI brain was notable for bilateral T2/FLAIR hyperintensities in the frontal and occipital lobes, which was concerning for leukodystrophy. Genetic testing returned positive for an ACSF3 mutation consistent with autosomal recessive combined malonic and methylmalonic aciduria. The patient was counseled to take vitamin B12 and L-Carnitine supplementation. Follow up MRI at 6 months showed complete resolution of white matter hyperintensities and the patient no longer complained of headache.  

Adult onset methylmalonic aciduria is rare. Prompt recognition and treatment with B12 and L-Carnitine supplementation can yield favorable outcomes. Continued monitoring of homocysteine, acylcarnitine, and methylmalonic acid at follow up, with adequate diet restricted of propionic amino acid precursors is imperative.