Introduction

Methylmalonic Aciduria (MMA) is a heterogeneous group of rare diseases leading to accumulation of methylmalonic acid in body fluids. One of the causes of the disease is the methylmalonic aciduria, cblA type (cblA – type MMA), conditioned by a mutation in the MMAA gene, which is essential for the proper functioning of a cofactor of the methylmalonyl-CoA mutase. The symptoms of the disease, depending on the cause, may manifest themselves at different ages. Most patients are sensitive to high doses of hydroxycobalamin, which is associated with better prognosis.

Material and method

The purpose of the study was to retrospectively analyze the clinical picture and effects of treatment of patients with methylmalonic aciduria related to mutation in the MMAA gene.

Results

Five patients with diagnosed cblA – type MMA were presented. At the time of diagnosis the median of age was 18.8 months, but the symptoms had already appeared since infancy, as recurrent vomiting and delayed psychomotor development. Significant excretion of methylmalonic acid in urine and metabolic acidosis traits with significantly increased anionic gap were observed in all patients. All of them were sensitive to the treatment with vitamin B₁₂. The median of therapy duration and observation is 12.2 years. During the treatment, good metabolic control was achieved in all patients, but their cognitive development is delayed. Three patients have renal failure and pharmacologically treated arterial hypertension.

Conclusions

Patients with a mutation in the MMAA gene are sensitive to treatment with hydroxocobalamine, but the inclusion of appropriate treatment does not protect against neurodevelopmental disorders and chronic kidney disease.

中文翻译：

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5例与MMAA突变相关的甲基丙二酸尿症患者的临床表现和治疗效果。

介绍

甲基丙二酸尿症 (MMA) 是一组异质的罕见疾病，可导致体液中甲基丙二酸的积累。该疾病的原因之一是甲基丙二酸尿症，cblA 型 ( cblA – MMA 型)，受MMAA基因突变的影响，这对于甲基丙二酰辅酶 A 变位酶的辅助因子的正常功能至关重要。根据病因，疾病的症状可能在不同年龄表现出来。大多数患者对高剂量的羟钴胺敏感，这与更好的预后有关。

材料和方法

本研究的目的是回顾性分析与MMAA基因突变相关的甲基丙二酸尿症患者的临床表现和治疗效果。

结果

介绍了 5 名诊断为 cblA – MMA 型的患者。诊断时的中位年龄为 18.8 个月，但症状从婴儿期就已经出现，反复呕吐和精神运动发育迟缓。在所有患者中均观察到尿中甲基丙二酸的显着排泄和具有显着增加的阴离子间隙的代谢性酸中毒特征。_{他们都对维生素B 12}治疗敏感。治疗持续时间和观察时间的中位数为 12.2 年。在治疗过程中，所有患者的代谢都得到了很好的控制，但他们的认知发展却有所延迟。三名患者患有肾功能衰竭和药物治疗的动脉高血压。

结论

MMAA基因突变的患者对羟钴胺治疗敏感，但纳入适当的治疗并不能预防神经发育障碍和慢性肾病。