Abstract:

Methylmalonic acidemia (MMA) is a relatively common inherited organic acid disorder. However, MMA-associated subacute combined degeneration of the spinal cord (SCD) in pediatric patients remains exceedingly rare, with insidious onset and high risk of diagnostic delay or misdiagnosis. This report presents a retrospective analysis of the clinical, neuroimaging, biochemical, and genetic features of an 8-year-old boy diagnosed with cblC-type MMA-homocysteinemia who developed SCD. The patient initially presented with progressive gait ataxia and had a documented history of global developmental delay, including language and motor milestones, and was previously diagnosed with mild intellectual disability. Neurological examination revealed bilateral lower-limb muscle strength of grade IV+, mild spasticity, impaired vibration and proprioception, reduced cortical sensation, and positive Romberg and heel-knee-shin tests. Laboratory tests showed significantly elevated levels of homocysteine, propionylcarnitine, and methylmalonic acid in the blood and urine. Whole-spine magnetic resonance imaging (MRI) demonstrated diffuse abnormal signals in the posterior columns of the thoracic spinal cord at the T5-T8 levels. Genetic testing confirmed compound heterozygous variations in the MMACHC gene, c.217C>T and c.365A>T, confirming the diagnosis of cbl C type MMA combined with homocysteinemia. After treatment with L-carnitine, vitamin B₆, betaine, and folic acid, the patient's neurological symptoms and signs completely resolved, gait returned to normal, and blood homocysteine and urine methylmalonic acid levels significantly decreased. MMA combined with homocysteinemia leading to SCD is relatively rare in children. Early diagnosis can be made by combining biochemical indicators, spinal cord MRI, and MMACHC gene testing. Timely intervention for the primary disease can significantly improve clinical manifestations, including SCD.

Key words: methylmalonic acidemia, homocystinemia, subacute combined degeneration, child