Servicio de Pediatria, Unidad de Enfermedades Metabólicas, Hospital Universitario Ramón y Cajal, IRYCIS, Crta de Colmenar Viejo, km 9,100, 28034, Madrid, Spain.
Unidad de Bioestadistica Clinica, Instituto Ramon y Cajal de Investigacion Sanitaria, CIBER Epidemiología y Salud Pública (CIBERESP), Hospital Universitario Ramón y Cajal, Crta de Colmenar Viejo, km 9,100, 28034, Madrid, Spain.
Orphanet J Rare Dis. 2021 May 18;16(1):226. doi: 10.1186/s13023-021-01865-7.
Propionic acidemia (PA), an inborn error of metabolism, is caused by a deficiency in propionyl-CoA carboxylase. Patients have to follow a diet restricted in the propiogenic amino acids isoleucine (Ile), valine (Val), methionine (Met) and threonine (Thr); proper adherence can prevent and treat acute decompensation and increase life expectancy. However, chronic complications occur in several organs even though metabolic control may be largely maintained. Bone marrow aplasia and anemia are among the more common.
In this retrospective study, data for patients with PA being monitored at the Hospital Ramón y Cajal (Madrid, Spain) (n = 10) in the past 10 years were examined to statistically detect relationships between persistent severe anemia outside of metabolic decompensation episodes and dietary practices such as natural protein intake and medical food consumption (special mixture of precursor-free amino acids) along with plasma levels of branched-chain amino acids (BCAA). High ferritin levels were deemed to indicate that a patient had received repeated transfusions for persistent anemia since data on hemoglobin levels at the moment of transfusion were not always passed on by the attending centers.
Three patients had severe, persistent anemia that required repeated blood transfusions. Higher medical food consumption and plasma Leu levels were associated with iron overload. Notably, natural protein intake and plasma Val were negatively correlated with ferritin levels. We also observed an inverse relationship between plasma Val/Leu and Ile/Leu ratios and ferritin.
The present results suggest that severe anemia in patients with PA might be associated with low natural protein intake and BCAA imbalance.
丙酸血症（PA）是一种先天性代谢缺陷病，由丙酰辅酶 A 羧化酶缺乏引起。患者必须遵循限制支链氨基酸（亮氨酸、缬氨酸、蛋氨酸和苏氨酸）摄入的饮食；适当的饮食可以预防和治疗急性失代偿，并延长预期寿命。然而，即使代谢控制得到很大程度的维持，也会在多个器官中发生慢性并发症。骨髓再生不良和贫血是较为常见的并发症。
在这项回顾性研究中，对过去 10 年来在西班牙马德里 Ramón y Cajal 医院（n=10）接受监测的 PA 患者的数据进行了检查，以统计检测在代谢失代偿发作之外持续严重贫血与饮食实践之间的关系，如天然蛋白质摄入和医学食品（无支链氨基酸预混物）的消耗，以及支链氨基酸（BCAA）的血浆水平。铁蛋白水平升高表明患者因持续性贫血接受了多次输血，因为并非所有中心都会提供输血时的血红蛋白水平数据。
有 3 名患者出现严重、持续性贫血，需要反复输血。更高的医学食品消耗和血浆亮氨酸水平与铁过载有关。值得注意的是，天然蛋白质摄入和血浆缬氨酸与铁蛋白水平呈负相关。我们还观察到血浆缬氨酸/亮氨酸和异亮氨酸/亮氨酸比值与铁蛋白之间存在负相关关系。
本研究结果表明，PA 患者的严重贫血可能与天然蛋白质摄入不足和 BCAA 失衡有关。
