Assessment of blood cobalt levels and safety of long-term hydroxocobalamin therapy in patients with cblC defect.

BACKGROUND: Hydroxocobalamin (OHCbl), the most effective form of vitamin B12 containing cobalt (Co) as its core component, is the mainstay therapy for cobalamin C (cblC) defect, yet long-term Co exposure and safety signals remain incompletely characterized. METHODS: We retrospectively analyzed 379 cblC patients receiving OHCbl therapy. Among them, 270 had prognostic data and 99 had laboratory and Co measurements. Adverse drug reactions (ADRs) were evaluated using the Naranjo scale. Regression models identified determinants of Co levels and associations of OHCbl dosage, treatment duration, and Co concentration with routine laboratory parameters, potential ADRs and prognosis. RESULTS: Median treatment duration was 76.70 months and median OHCbl dosage was 1.07 mg/kg/week; Median blood Co concentration was 22.53 μg/L. Although 53.54% of patients having Co >20.00 μg/L, no severe Co toxicity was observed. OHCbl dosage was the only independent predictor of Co (β = 0.70, p < 0.001). In adjusted analyses of 29 routine laboratory indicators, no association with OHCbl dosage, treatment duration, or blood Co remained significant after Benjamini-Hochberg false discovery rate correction (all q > 0.05). ADRs occurred in 82.6% of patients, most commonly chromaturia (80.39%), psychomotor agitation (8.84%), and localized rash (5.52%), and were predominantly mild and self-limited. Higher OHCbl dosage was associated with increased odds of any potential ADR (OR = 3.61) and chromaturia (OR = 3.00); longer treatment duration was independently associated with better overall prognosis (OR = 1.02), and no associations with injury to specific organ systems were detected. CONCLUSION: OHCbl remains well tolerated even with prolonged, higher-dosage treatment, supporting its continued long-term use with routine monitoring.