Severe anemia in patients with Propionic acidemia is associated with branched-chain amino acid imbalance

Abstract

Background 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. Materials and methods 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. Results 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. Conclusion The present results suggest that severe anemia in patients with PA might be associated with low natural protein intake and BCAA imbalance.

Interorgan amino acid interchange in propionic acidemia: the missing key to understanding its physiopathology

“…The effect of excessive restriction of these amino acids goes beyond that. We have previously demonstrated that low Val levels can also be related to the chronic anemia that some of these patients suffer (Stanescu et al 2021 ). Low Val and Ile levels in relation with high Leu concentrations is the usual scenario in PA (Molema et al 2019 ) and has recently been related to various deleterious mechanisms in maple syrup urine disease patients (Strauss et al 2020 ).…”

Effects of Soy–Whey Protein Nutritional Supplementation on Hematopoiesis and Immune Reconstitution in an Allogeneic Transplanted Mice

“…These data suggested that post-BMT, DP supplementation promotes hematopoietic stem/progenitor cell differentiation by reverting overall malnutrition. Protein malnutrition may also result from either the inadequate consumption of branched-chain amino acids (BCAAs) or a BCAA metabolism imbalance [ 52 , 53 ]. Wilkinson et al reported that reduced BCAA levels inhibited hematopoietic stem cell proliferation and survival in vitro and rendered these cells incapable of sustaining normal physiological activity in vivo [ 54 ].…”

Organic Acidemias: Clinical Presentation in Neonates

“…In anemic infants, erythropoietin can be considered but is often not effective. 101 Current evidence favors liver transplant as the eventual, effective treatment. 102 Figure 8 shows the key principles of management.…”