Abstract:

Objective To discuss the clinical phenotype and genotype characteristics of two pediatric patients with late-onset methylmalonic acidemia （MMA） cblC type， and to provide the basis for early clinical recognition of MMA. Methods The clinical data of two pediatric patients with late-onset MMA cblC type were collected， including clinical phenotypes， biochemical detection results， blood and urine organic acid analyses， neuroimaging， electroencephalograms， genotypes and so on. The characteristics of the disease were analyzed in combination with the related literature review. Results Both pediatric patients were female， with onset in adolescence. Patient 1 presented with psychiatric symptoms， while pediatric patient 2 presented with cognitive impairment. Both pediatric patients experienced weakness in both lower limbs and speech disorders. At initial diagnosis， the serum homocysteine （Hcy） levels were severely increased， the urine methylmalonic acid levels were increased， the brain magnetic resonance imaging results indicated brain atrophy， and the electroencephalogram results showed the increased slow wave activity in both cerebral hemispheres. The pediatric patient 2 exhibited epileptiform discharges in bilateral frontal and temporal regions. The genetic testing results showed the c.482G>A mutation in the MMACHC gene. Both two pediatric patients were treated with intramuscular injections of vitamin B12， along with oral folic acid， vitamin B6， levocarnitine， and betaine. The symptoms of two patierts were improved， the serum Hcy levels were decreased， and the urine methylmalonic acid levels returned to normal. Conclusion The phenotype of late-onset MMA cblC type is diverse， primarily involving neuropsychiatric impairment， with the c.482G>A mutation being the most common genotype. The increasing of serum Hcy levels and brain atrophy can serve as the biomarkers for the early recognition of late-onset cblC type pediatric patients.

Key words: Methylmalonic acidaemia, Autoimmune encephalitis, Homocysteine, Brain atrophy, Genotype