Long term follow-up of the dietary intake in propionic acidemia

Abstract

Long-term dietary management of Propionic acidemia (PA) includes natural protein restriction, and supplementation with medical formula enriched with leucine (Leu) and free of valine (Val), isoleucine (Ileu), methionine (Met), and threonine (Thr). As PA medical formulas have high leucine content, concerns started to arise regarding potential long-term health risks of unbalanced leucine intake. PA patients have chronically low plasma levels of Ile and Val, which led to the paradoxical need to supplement with propiogenic single amino acids (AAs). Our report takes a retrospective look at the long-term dietary management of four patients and its reflection on their plasma amino acids. The patients' total protein intake was above the recommended dietary allowance (RDA) and had a high Leu/Val and Leu/Ile intake ratios in diet. Despite adequate total protein intake, patients had chronically low plasma Ile and Val and a high plasma Leu/Val and Leu/Ile ratios, which could be attributed to high Leu intake. We conclude that the best approach to PA dietary management is to only use medical formula with patients not meeting their RDA through natural protein, and to monitor plasma amino acids levels closely.

Prevalence of propionic acidemia in China

“…However, the primary aim of treatment for PA is to prevent protein catabolism and maintain biochemical control, growth, and development through adequate calorie intake. Long-term dietary management of PA involves restricting natural protein and supplementing with medical formulas that are enriched with Leu but free of Val, Ile, Met, and Thr to reduce the concentration of elevated metabolites [ 69 ]. Recent studies have suggested that the medical formula used for PA patients may contribute to growth retardation, despite high total protein intake.…”

Fasting alleviates metabolic alterations in mice with propionyl-CoA carboxylase deficiency due to Pcca mutation

“…Notably, propionate, primarily produced by the microbiome, and propiogenic amino acids, obtained through dietary sources, are the main contributors to propionyl-CoA production 28 . Consequently, the use of antibiotics to suppress propionate production from the microbiome and the adoption of a protein-restricted diet to reduce propiogenic amino acids are proven effective strategies in alleviating metabolic alterations and improving outcomes in PA disease [29][30][31][32][33][34] .Extended fasting is typically discouraged for patients with PA due to the belief that fasting may stimulate the oxidation of odd-chain fatty acids and amino acid catabolism to propionyl-CoA, which potentially exacerbates metabolic crises 17,35,36 . However, this recommendation lacks comprehensive…”

“…Notably, propionate, primarily produced by the microbiome, and propiogenic amino acids, obtained through dietary sources, are the main contributors to propionyl-CoA production 28 . Consequently, the use of antibiotics to suppress propionate production from the microbiome and the adoption of a protein-restricted diet to reduce propiogenic amino acids are proven effective strategies in alleviating metabolic alterations and improving outcomes in PA disease [29][30][31][32][33][34] .…”