Analysis of hydroxocobalamin dosage in patients with CblC deficiency.

Objective: cblC deficiency is the most common organic acidemia in China. Hydroxocobalamin (OHCbl) is the main important therapeutic approach, while no approved protocols on its dosage during stable periods exist. This study aims to analyze OHCbl dosage and explore its influencing factors, providing reference for the option of OHCbl dosage.

Methods: A total of 730 patients with cblC deficiency during stable periods were enrolled. Univariate analysis and multiple linear regression analysis were used to investigate the correlation between OHCbl dosage and tandem mass spectrometry (MS/MS)-based newborn screening (NBS), disease onset as well as MMACHC gene mutation.

Results: Univariate analysis revealed no significant difference in OHCbl dosage between whether patients were diagnosed by MS/MS-based NBS or not, while significant differences were found based on disease onset and the presence of c.482G > A variant. Multiple linear regression analysis further identified disease onset and the c.482G > A variant as independent factors influencing OHCbl dosage. The median OHCbl dosage during stable periods was 1.18 mg/kg/week, with 0.31 mg/kg/week in patients with the c.482G > A variant and 1.37 mg/kg/week in those without. However, in patients carrying the c.482G > A variant, there was no significant difference in the OHCbl dosage between those with and without disease onset, while in patients without the c.482G > A variant, those with disease onset had a higher OHCbl dosage compared to those without.

Conclusion: The study demonstrated the independent influencing factors of OHCbl dosage in patients with cblC deficiency and put forward corresponding reference for the option of OHCbl dosage.