Clinical feature and outcome of late-onset cobalamin C disease patients with neuropsychiatric presentations: a Chinese case series.

Objective: The Cobalamin C (cblC) disease is an inborn error of cobalamin metabolism. Late-onset cblC disease was diagnosed in patients having overt symptoms after 4 years of age. The late-onset cblC disease patients were rare and easily misdiagnosed. This study analyzed the clinical presentations, gene mutations, and treatments of Chinese patients with late-onset cblC disease.

Methods: The clinical data of 26 Han Chinese patients diagnosed with late-onset cblC disease were retrospectively analyzed. All patients underwent serum homocysteine level exam, urine concentrations of organic acids measurement, neuroimaging scans, gene analysis, and treatments evaluations.

Results: The mean age at disease onset and diagnosis was 17.8±7.0 years. The most frequent neuropsychiatric disturbances were lower limb weakness (50%), psychiatric disturbances (46.2%), and gait instability (42.3%). The mean methylmalonic acid level in urine was 107.4±56.6 μmol/L, and mean serum total homocysteine was 105.4±41.0 μmol/L. The most common abnormal radioimaging changes were observed in the spinal cord (88%) and brain (32%). Scoliosis was detected in 85.7% of patients. The methylmalonic aciduria and homocystinuria type C protein gene analysis showed that c.482G>A (57.7%) and c.609G>A (34.6%) mutations were the most frequent genotypes. After treatments with hydroxycobalamin, betaine, folic acid, L-carnitine, and compound vitamin B, the clinical features and biochemical parameters of patients with late-onset cblC disease were found to be alleviated.

Conclusion: In our late-onset cblC disease cases, lower limb weakness, psychiatric disturbances, and gait instability were the most frequent manifestations. Patients responded well to the drug treatments with hydrocobalamin and betaine. When juvenile or adult patients with hyperhomocysteinemia present with neurological symptoms, cblC disease needs to be considered.