Hydroxocobalamin dose escalation improves metabolic control in cblC.
Hydroxocobalamin dose escalation improves metabolic control in cblC.
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DOI：
10.1007/s10545-009-1257-y
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发表时间：
2009-12
影响因子：
4.2
通讯作者：
Venditti, C. P.
中科院分区：
文献类型：
--
作者：
Carrillo-Carrasco, N.;Sloan, J.;Valle, D.;Hamosh, A.;Venditti, C. P.
钴胺素C（cblC）是甲基丙二酸血症和高同型半胱氨酸血症的组合形式，被认为是细胞内钴胺素代谢最常见的先天性缺陷。这种情况可以通过扩大新生儿筛查来检测，并且如果没有怀疑和及时治疗，可能会有危及生命的急性新生儿表现。肌内注射（IM）羟钴胺素（OHCbl）是cblC患者的主要治疗方法，但不存在正式的剂量指南。通常在开始治疗后观察到临床改善和血浆甲基丙二酸（MMA）和总同型半胱氨酸（tHcy）水平降低，以及甲硫氨酸增加。众所周知，尽管进行了治疗，但仍可能发生长期并发症，如发育迟缓和进行性视力丧失。我们描述了一个13岁男孩的生化反应恶化的代谢参数，尽管严格遵守常规治疗方案。我们将OHCbl剂量从每天1 mg IM逐渐增加至20 mg IM，并观察到剂量依赖性反应，血浆MMA降低80%。（25至5.14 μmol/L;正常范围<0.27 μmol/L），tHcy降低55%（112 - 50 μmol/L;正常范围：0-13 μmol/L）和蛋氨酸增加2倍以上（17 - 36 μmol/L;正常范围：7-47 μmol/L）。这表明，可能需要更高的OHCbl剂量来实现cblC患者的最佳生化反应，但尚不清楚它是否可以减缓或消除其他并发症。未来的临床试验，以确定更高剂量的OHCbl治疗cblC和其他细胞内钴胺素代谢疾病的患者的好处，应计划。
Cobalamin C (cblC), a combined form of methylmalonic acidaemia and hyperhomocysteinaemia, is recognized as the most frequent inborn error of intracellular cobalamin metabolism. This condition can be detected by expanded newborn screening and can have an acute neonatal presentation that is life-threatening if not suspected and promptly treated. Intramuscular (IM) hydroxocobalamin (OHCbl) is the main treatment for patients with cblC, but formal dosing guidelines do not exist. A clinical improvement and a decrease of plasma methylmalonic acid (MMA) and total homocysteine (tHcy) levels, and an increase in methionine are typically observed after its initiation. It is well recognized that despite treatment, long-term complications such as developmental delay and progressive visual loss, may still develop. We describe the biochemical response of a 13-year-old boy with worsening metabolic parameters despite strict adherence to a conventional treatment regimen. We progressively increased the OHCbl dose from 1 to 20 mg IM per day and observed a dose-dependent response with an 80% reduction of plasma MMA (25 to 5.14 μmol/L; normal range <0.27 μmol/L), a 55% reduction of tHcy (112 to 50 μmol/L; normal range: 0–13 μmol/L) and a greater than twofold increase in methionine (17 to 36 μmol/L; normal range: 7–47 μmol/L). This suggests that higher OHCbl doses might be required to achieve an optimal biochemical response in cblC patients, but it is unknown whether it may slow or eliminate other complications. Future clinical trials to determine the benefits of higher-dose OHCbl therapy in patients with cblC and other disorders of intracellular cobalamin metabolism should be planned.
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