Molecular genetics and metabolism · 2026
Hydroxocobalamin monotherapy in patients with cblC deficiency: Biochemical analysis and clinical observations.
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Ding Si, Hao Lili, Ding Yi, Deng Yuxin, Chen Ting, Zhan Xia, Xu Peng, Yang Chiju, Zou Hui, Chen Yongxing, Wu Shengnan, Wang Yufeng, Yang Min, Liang Lili, Han Lianshu
Аннотация
BACKGROUND: Cobalamin C (cblC) deficiency is the most frequent disease involving intracellular cobalamin metabolism. This study evaluates the response of hydroxocobalamin (OHCbl) monotherapy in patients with stable cblC disease, aiming to simplify treatment strategies.
METHODS: This retrospective cohort study enrolled cblC patients with a follow-up duration exceeding six months. Clinical features and biochemical markers were assessed before and after OHCbl monotherapy. Genotype-stratified analyses were further performed. Propensity score matching (PSM,1:1) was applied to identify control patients receiving combined therapy (OHCbl plus oral agents), based on disease onset status, OHCbl dosage, and genotype.
RESULTS: Forty-one patients received OHCbl monotherapy for a median duration of 33.0 months. At last follow-up, 39 patients remained reportedly asymptomatic, while two had a poor prognosis. All patients achieved total homocysteine (tHcy)levels≤50 μmol/L and normal free carnitine (C0) levels, accompanied by significant improvements in other metabolic biomarkers. Compared to severe genotypes, patients with mild genotypes required lower OHCbl doses (P = 0.001) but showed no significant differences in the last-visit methionine and tHcy levels and outcomes (P > 0.05). Among 125 patients who switched from combination therapy to OHCbl monotherapy, ten showed clinical improvements after a median treatment duration of 9.2 months, while 115 patients exhibited no change (58 remained reportedly asymptomatic and 57 had persistent complications). Of these, 111 achieved tHcy≤50 μmol/L and tended to have shorter durations of prior combined therapy, lower tHcy levels during treatment, and a higher frequency of milder genotypes. PSM yield 28 matched pairs. No significant differences were observed in demographics, OHCbl dosage, outcomes or most biochemical markers (P>0.05), except for lower post-treatment C0, propionyl carnitine and methionine levels in the monotherapy group (P<0.05).
CONCLUSION: Evidence suggests that in cblC deficiency, OHCbl monotherapy was associated with favorable reported clinical status and sustained biochemical control particularly in milder genotypes, and may represent a practicable simplified treatment strategy. However, extrapolation to more severe genotypes should be cautioned due to the limited case numbers in this study.
METHODS: This retrospective cohort study enrolled cblC patients with a follow-up duration exceeding six months. Clinical features and biochemical markers were assessed before and after OHCbl monotherapy. Genotype-stratified analyses were further performed. Propensity score matching (PSM,1:1) was applied to identify control patients receiving combined therapy (OHCbl plus oral agents), based on disease onset status, OHCbl dosage, and genotype.
RESULTS: Forty-one patients received OHCbl monotherapy for a median duration of 33.0 months. At last follow-up, 39 patients remained reportedly asymptomatic, while two had a poor prognosis. All patients achieved total homocysteine (tHcy)levels≤50 μmol/L and normal free carnitine (C0) levels, accompanied by significant improvements in other metabolic biomarkers. Compared to severe genotypes, patients with mild genotypes required lower OHCbl doses (P = 0.001) but showed no significant differences in the last-visit methionine and tHcy levels and outcomes (P > 0.05). Among 125 patients who switched from combination therapy to OHCbl monotherapy, ten showed clinical improvements after a median treatment duration of 9.2 months, while 115 patients exhibited no change (58 remained reportedly asymptomatic and 57 had persistent complications). Of these, 111 achieved tHcy≤50 μmol/L and tended to have shorter durations of prior combined therapy, lower tHcy levels during treatment, and a higher frequency of milder genotypes. PSM yield 28 matched pairs. No significant differences were observed in demographics, OHCbl dosage, outcomes or most biochemical markers (P>0.05), except for lower post-treatment C0, propionyl carnitine and methionine levels in the monotherapy group (P<0.05).
CONCLUSION: Evidence suggests that in cblC deficiency, OHCbl monotherapy was associated with favorable reported clinical status and sustained biochemical control particularly in milder genotypes, and may represent a practicable simplified treatment strategy. However, extrapolation to more severe genotypes should be cautioned due to the limited case numbers in this study.