Burlina Alberto B, Burlina Alessandro P, Mignani Renzo, Cazzorla Chiara, Gueraldi Daniela, Puma Andrea, Loro Christian, Baumgartner Matthias R, Gragnaniello Vincenza
Division of Inherited Metabolic Diseases, Department of Women's and Children's Health University Hospital of Padua Padua Italy.
Division of Inherited Metabolic Diseases, Department of Women's and Children's Health University of Padua Padua Italy.
JIMD Rep. 2024 Jan 10;65(2):56-62. doi: 10.1002/jmd2.12411. eCollection 2024 Mar.
Methylmalonic acidemia cblB type (MMA cblB) is an autosomal recessive inborn error of amino acid metabolism that results in impaired synthesis of adenosylcobalamin, a cofactor of methylmalonyl-CoA mutase. It presents with episodes of coma, vomiting, hypotonia, metabolic acidosis, and hyperammonemia. End-stage kidney disease is a long-term complication. Treatments include vitamin B12 supplementation, L-carnitine, and a low-protein diet. Liver, kidney, or combined liver-kidney transplantations are promising options, but they are not without complications. We report a patient suffering from MMA cblB who developed end-stage kidney disease at 18 years of age. Kidney transplantation allowed him to recover normal kidney function and good metabolic control. Unfortunately, after two decades, he developed non-Hodgkin lymphoma and severe chemotherapy toxicity which led to his death. The risk of lymphoproliferative diseases is known to increase after solid organ transplantation. However, in MMA, factors including mitochondrial dysfunction and oncometabolites, may further increase the risk of malignancy and drug toxicity. Our report highlights the importance of considering the increased risk of cancer in long-term follow-up of MMA cblB patients, especially after solid organ transplantation. Moreover, when chemotherapy is needed, the increased risk of toxicity and metabolic decompensation should be considered and monitored.
甲基丙二酸血症cblB型(MMA cblB)是一种常染色体隐性遗传性氨基酸代谢紊乱疾病,可导致甲基丙二酰辅酶A变位酶的辅因子腺苷钴胺素合成受损。其临床表现为昏迷、呕吐、肌张力减退、代谢性酸中毒和高氨血症发作。终末期肾病是一种长期并发症。治疗方法包括补充维生素B12、左旋肉碱和低蛋白饮食。肝移植、肾移植或肝肾联合移植是有前景的选择,但也并非没有并发症。我们报告了一名患有MMA cblB的患者,他在18岁时发展为终末期肾病。肾移植使他恢复了正常肾功能并实现了良好的代谢控制。不幸的是,二十年后,他患上了非霍奇金淋巴瘤并出现严重的化疗毒性反应,最终导致死亡。已知实体器官移植后淋巴增殖性疾病的风险会增加。然而,在MMA中,包括线粒体功能障碍和肿瘤代谢物在内的因素可能会进一步增加恶性肿瘤和药物毒性的风险。我们的报告强调了在MMA cblB患者的长期随访中,尤其是在实体器官移植后,考虑癌症风险增加的重要性。此外,当需要进行化疗时,应考虑并监测毒性增加和代谢失代偿的风险。