Division of Metabolism and Children's Research Center, University Children's Hospital, Zurich, Switzerland; Institute of Physiology, University of Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Switzerland; radiz - Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Switzerland.
Mol Genet Metab. 2013 Dec;110(4):472-6. doi: 10.1016/j.ymgme.2013.08.021. Epub 2013 Sep 17.
Chronic renal failure is a well-known long-term complication of methylmalonic aciduria (MMA-uria), occurring even under apparently optimal metabolic management. The onset of renal dysfunction seems to be dependent on the type of defect and vitamin B12-responsiveness. We report on a patient with a vitamin B12-responsive cobalamin A type (cblA) MMA-uria caused by a homozygous stop mutation (p.R145X) in the cobalamin A gene (MMAA). She was diagnosed with chronic kidney disease (CKD) stage III at the age of 12 years. Following re-evaluation, the patient received vitamin B12 (hydroxocobalamin) treatment, resulting in a significant decrease in the concentration of methylmalonic acid (MMA) in urine and plasma. Until age 29 years glomerular filtration rate remained stable probably due to hydroxocobalamin treatment slowing down progression to end-stage renal failure. Kidney biopsies showed non-specific manifestations of chronic interstitial inflammation. The patient received a renal transplant at age 35 years. Under continuous treatment with hydroxocobalamin there is no evidence of kidney damage due to MMA-uria until the last follow-up 6 years after transplantation. This case report illustrates (i) a long-term follow-up of a patient with MMA-uria due to cblA deficiency, (ii) the involvement of the kidney as a target organ and (iii) the importance of early and adequate vitamin B12 substitution in responsive patients. Further investigation will be necessary to prove the protective effect of hydroxocobalamin in the kidney in vitamin B12-responsive patients.
慢性肾衰竭是甲基丙二酸尿症（MMA-uria）的一种已知的长期并发症，即使在代谢管理明显优化的情况下也会发生。肾功能障碍的发生似乎取决于缺陷的类型和维生素 B12 的反应性。我们报告了一例维生素 B12 反应型钴胺素 A 型（cblA）MMA-uria 患者，其病因是钴胺素 A 基因（MMAA）的纯合终止突变（p.R145X）。她在 12 岁时被诊断为慢性肾脏病（CKD）III 期。重新评估后，患者接受了维生素 B12（羟钴胺）治疗，导致尿液和血浆中甲基丙二酸（MMA）的浓度显著降低。直到 29 岁，肾小球滤过率保持稳定，可能是由于羟钴胺治疗减缓了终末期肾衰竭的进展。肾活检显示非特异性慢性间质炎症表现。患者在 35 岁时接受了肾移植。在持续接受羟钴胺治疗的情况下，直到移植后最后一次随访的 6 年，都没有 MMA-uria 导致的肾脏损害的证据。本病例报告说明了（i）cblA 缺乏引起的 MMA-uria 患者的长期随访，（ii）肾脏作为靶器官的参与，以及（iii）对有反应的患者进行早期和充分的维生素 B12 替代的重要性。需要进一步的研究来证明在维生素 B12 反应性患者中，羟钴胺在肾脏中的保护作用。
