Fraser Jamie L, Venditti Charles P
aDivision of Genetics and Metabolism, Children's National Medical Center, Washington, District of Columbia bMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Pediatr. 2016 Dec;28(6):682-693. doi: 10.1097/MOP.0000000000000422.
Recent clinical studies and management guidelines for the treatment of the organic acidopathies methylmalonic acidemia (MMA) and propionic acidemia address the scope of interventions to maximize health and quality of life. Unfortunately, these disorders continue to cause significant morbidity and mortality due to acute and chronic systemic and end-organ injury.
Dietary management with medical foods has been a mainstay of therapy for decades, yet well controlled patients can manifest growth, development, cardiac, ophthalmological, renal, and neurological complications. Patients with organic acidopathies suffer metabolic brain injury that targets specific regions of the basal ganglia in a distinctive pattern, and these injuries may occur even with optimal management during metabolic stress. Liver transplantation has improved quality of life and metabolic stability, yet transplantation in this population does not entirely prevent brain injury or the development of optic neuropathy and cardiac disease.
Management guidelines should identify necessary screening for patients with methylmalonic acidemia and propionic acidemia, and improve anticipatory management of progressive end-organ disease. Liver transplantation improves overall metabolic control, but injury to nonregenerative tissues may not be mitigated. Continued use of medical foods in these patients requires prospective studies to demonstrate evidence of benefit in a controlled manner.
近期关于有机酸血症(甲基丙二酸血症(MMA)和丙酸血症)治疗的临床研究及管理指南阐述了旨在最大化健康水平和生活质量的干预措施范围。遗憾的是,由于急慢性全身及终末器官损伤,这些疾病仍会导致显著的发病率和死亡率。
几十年来,使用特殊医学用途食品进行饮食管理一直是治疗的主要手段,但病情得到良好控制的患者仍可能出现生长、发育、心脏、眼科、肾脏及神经方面的并发症。有机酸血症患者会遭受代谢性脑损伤,这种损伤以独特的模式靶向基底神经节的特定区域,即使在代谢应激期间进行最佳管理,这些损伤仍可能发生。肝移植改善了生活质量和代谢稳定性,但该人群的移植并不能完全预防脑损伤或视神经病变及心脏病的发生。
管理指南应确定对甲基丙二酸血症和丙酸血症患者进行必要筛查,并改善对进行性终末器官疾病的预期管理。肝移植可改善整体代谢控制,但对不可再生组织的损伤可能无法减轻。在这些患者中持续使用特殊医学用途食品需要前瞻性研究,以有控制的方式证明其益处。