Amino acid metabolism in patients with propionic acidaemia.
Propionic acidaemia (PA) is an inborn error of intermediary metabolism caused by deficiency of propionyl-CoA carboxylase. The metabolic block leads to a profound failure of central metabolic pathways, including the urea and the citric acid cycles. This review will focus on changes in amino acid metabolism in this inborn disorder of metabolism. The first noted disturbance of amino acid metabolism was hyperglycinaemia, which is detectable in nearly all PA patients. Additionally, hyperlysinaemia is a common observation. In contrast, concentrations of branched chain amino acids, especially of isoleucine, are frequently reported as decreased. These non-proportional changes of branched-chain amino acids (BCAAs) compared with aromatic amino acids are also reflected by the Fischer's ratio (concentration ratio of BCAAs to aromatic amino acids), which is decreased in PA patients. As restricted dietary intake of valine and isoleucine as precursors of propionyl-CoA is part of the standard treatment in PA, decreased plasma concentrations of BCAAs may be a side effect of treatment. The concentration changes of the nitrogen scavenger glutamine have to be interpreted in the light of ammonia levels. In contrast to other hyperammonaemic syndromes, in PA plasma glutamine concentrations do not increase in hyperammonaemia, whereas CSF glutamine concentrations are elevated. Despite lactic acidaemia in PA patients, hyperalaninaemia is only rarely reported. The mechanisms underlying the observed changes in amino acid metabolism have not yet been elucidated, but most of the changes can be at least partly interpreted as consequence of disturbance of anaplerosis.
Department of Paediatrics IV, Division of Neonatology, Neuropaediatrics and Inherited Metabolic Disorders, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. sabine.scholl-buergi@uki.at
Sabine
S
Scholl-Bürgi
Jörn Oliver
JO
Sass
Johannes
J
Zschocke
Daniela
D
Karall
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000641:Ammonia / Q000097:blood; D002952:Citric Acid Cycle; D004032:Diet; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D043586:Methylmalonyl-CoA Decarboxylase / Q000378:metabolism; D008954:Models, Biological; D056693:Propionic Acidemia / Q000175:diagnosis* / Q000235:genetics*; D014508:Urea / Q000378:metabolism; D014633:Valine / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D007532:Isoleucine; D005973:Glutamine; D000641:Ammonia; D014508:Urea; D043586:Methylmalonyl-CoA Decarboxylase; D014633:Valine; D008239:Lysine; D005998:Glycine