Wesół-Kucharska Dorota, Kaczor Magdalena, Pajdowska Magdalena, Ehmke Vel Emczyńska-Seliga Ewa, Bogdańska Anna, Kozłowski Dariusz, Piekutowska-Abramczuk Dorota, Ciara Elżbieta, Rokicki Dariusz
Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's, Health Institute, Warsaw, Poland.
Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland.
Mol Genet Metab Rep. 2020 Jan 8;22:100559. doi: 10.1016/j.ymgmr.2019.100559. eCollection 2020 Mar.
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 ( - type MMA), conditioned by a mutation in the 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.
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 gene.
Five patients with diagnosed - 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 B. 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.
Patients with a mutation in the gene are sensitive to treatment with hydroxocobalamine, but the inclusion of appropriate treatment does not protect against neurodevelopmental disorders and chronic kidney disease.
甲基丙二酸尿症（MMA）是一组导致甲基丙二酸在体液中蓄积的罕见异质性疾病。该疾病的病因之一是甲基丙二酸尿症cblA类型（-型MMA），由基因中的突变引起，该基因对于甲基丙二酰辅酶A变位酶的辅因子正常发挥功能至关重要。根据病因不同，该疾病的症状可能在不同年龄段出现。大多数患者对高剂量的羟钴胺敏感，这与较好的预后相关。
本研究的目的是回顾性分析与基因中突变相关的甲基丙二酸尿症患者的临床表现和治疗效果。
报告了5例确诊为-型MMA的患者。确诊时的年龄中位数为18.8个月，但症状自婴儿期就已出现，如反复呕吐和精神运动发育迟缓。所有患者均观察到尿中甲基丙二酸大量排泄以及代谢性酸中毒特征，阴离子间隙显著增加。他们均对维生素B治疗敏感。治疗持续时间和观察的中位数为12.2年。治疗期间，所有患者均实现了良好的代谢控制，但认知发育延迟。3例患者出现肾衰竭并接受药物治疗的动脉高血压。
基因中存在突变的患者对羟钴胺治疗敏感，但采用适当治疗并不能预防神经发育障碍和慢性肾病。
