Changes in plasma amino acid concentrations with increasing age in patients with propionic acidemia

Abstract

The objective of the study is to analyze plasma amino acid concentrations in propionic acidemia (PA) for the purpose of elucidating possible correlations between propionyl-CoA carboxylase deficiency and distinct amino acid behavior. Plasma concentrations of 19 amino acids were measured in 240 random samples from 11 patients (6 families) with enzymatically and/or genetically proven propionic acidemia (sampling period, January 2001-December 2007). They were compared with reference values from the literature and correlated with age using the Pearson correlation coefficient test. Decreased plasma concentrations were observed for glutamine, histidine, threonine, valine, isoleucine, leucine, phenylalanine and arginine. Levels of glycine, alanine and aspartate were elevated, while values of serine, asparagine, ornithine and glutamate were normal. For lysine, proline and methionine a clear association was not possible. Significant correlations with age were observed for 13 amino acids (positive correlation: asparagine, glutamine, proline, alanine, histidine, threonine, methionine, arginine; negative correlation: leucine, phenylalanine, ornithine, glutamate and aspartate). This study gives new insight over long-term changes in plasma amino acid concentrations and may provide options for future therapies (e.g., substitution of anaplerotic substances) in PA patients.

Autism in patients with propionic acidemia

“…However, we did find a very interesting alteration, low normal serum valine levels and a decreased valine to leucine ratio, detected in the majority of our patients. Similar results have been previously documented in PA [15] and MMA and may be a consequence of supplementation with leucine enriched, precursor free amino acid mixture (Manoli et al, Genetics in Med 2016). Additionally, the primary enzymatic defect affects intra-mitochondrial physiology which, in the neuron, is impossible to monitor with standard metabolic methods.…”

Single amino acid supplementation in aminoacidopathies: a systematic review

“…As in MMA, deficiencies of both isoleucine and valine are often observed [25,30]. In addition, Scholl-Bürgi et al showed that blood isoleucine and valine concentrations, in contrast to almost all other amino acids, did not correlate with age [31]. To prevent a relative isoleucine deficiency, the use of routine isoleucine supplementation (100 mg/d) has been reported [32].…”

Advances and challenges in the treatment of branched‐chain amino/keto acid metabolic defects

“…Direct effects of toxic metabolites, particularly free organic acids and the various acyl-CoA metabolites, on key enzymes of intermediary metabolism help to explain findings such as acidosis, hypo-glycemia and hyperammonemia in acutely decompensated patients with branched-chain amino-/organic acidopathies. For example, enzyme inhibition can affect α-ketoglutarate dehydrogenase and pyruvate dehydrogenase (Sauer et al 2008), carbamyl-phosphate synthetase (Martin-Requero et al 1983), N-acetyl-glutamate synthetase (Stewart and Walser, 1980) creatine kinase and others (Schuck et al 2004; Scholl-Bürgi et al 2010). …”

“…Providing energy and protein at intakes required by patients with growth deficiency and catch-up growth needs may result in improved growth and adequate nutritional status (Yannicelli et al 2003). In patients with PA, changes in plasma AA concentrations have been related to age, nutritional supply and metabolic state (Scholl-Bürgi et al 2010). A European multicenter study on 183 patients with MMA revealed a huge variation in the management of these patients regarding total and natural protein intake, special AA substitutes and adjunct medication (Zwickler et al 2008).…”

“…Essentially, anaplerotic precursors replenish metabolite levels depleted within the Krebs cycle (Scholl-Bürgi et al 2010; Brunengraber and Roe, 2006). Considering the various secondary mitochondrial effects in patients with ‘classical’ forms, there may be therapeutic value for anaplerotic substances.…”