Background

Methylmalonic acidaemia with homocystinuria type C (cblC defect) is an inherited error of cobalamin metabolism. Cobalamin deficient processing results in high levels of methylmalonic acid and homocysteine. The latter is considered to be a risk factor for multiple sclerosis (MS). We report on the first case of a patient with comorbid cblC defect and MS.

Case report

This young male presented at the age of 14 with a relapsing-remitting neurological disorder associated with imaging alterations suggestive of MS. Treatment resulted in a partial clinical improvement with vanishing of white matter lesions. Later on, the emergence of unexpected clinical features led to a metabolic work-up, revealing a cobalamin intracellular defect. Genetic analysis disclosed a single variant in MMACHC (c.482G > A; p.Arg161Gln) and another splicing variant in PRDX1 (c.1-515G > T) that cause the silencing of the wild-type MMACHC allele, so confirming the diagnosis of cblC defect. Although cblC treatment was effective, when 17-year-old he experienced a relapse of neurological symptoms. Further imaging and laboratory studies eventually supported the diagnosis of MS.

Discussion

While the comorbid association of MS and cblC in our patient may remain anecdotic, we suggest measuring Hcy and MMA levels in young patients with a relapsing-remitting demyelinating disorder, in order not to miss a cblC defect, that requires a specific and effective treatment.

中文翻译：

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一名年轻男性的多发性硬化症和细胞内钴胺素缺陷 (MMACHC/PRDX1) 合并症。

背景

C 型高胱氨酸尿症（cblC 缺陷）的甲基丙二酸血症是钴胺素代谢的遗传错误。钴胺素缺乏加工会导致高水平的甲基丙二酸和同型半胱氨酸。后者被认为是多发性硬化症 (MS) 的危险因素。我们报告了第一例伴有 cblC 缺陷和 MS 的患者。

案例报告

这名年轻男性在 14 岁时出现了与提示 MS 的影像学改变相关的复发缓解型神经系统疾病。治疗导致部分临床改善，白质病变消失。后来，意外临床特征的出现导致代谢检查，揭示了钴胺素细胞内缺陷。遗传分析揭示了MMACHC中的单个变体(c.482G > A; p.Arg161Gln) 和 PRDX1 中的另一个剪接变体( c.1-515G > T) 导致野生型MMACHC沉默等位基因，从而确认cblC缺陷的诊断。尽管 cblC 治疗是有效的，但当他 17 岁时，他经历了神经系统症状的复发。进一步的影像学和实验室研究最终支持了 MS 的诊断。

讨论

虽然我们的患者中 MS 和 cblC 的共病关联可能仍然是轶事，但我们建议测量患有复发-缓解型脱髓鞘疾病的年轻患者的 Hcy 和 MMA 水平，以免错过 cblC 缺陷，这需要特定和有效的治疗。