There are stills unknowns about the treatment outcomes and the risk of decompensation episodes (DEs), usually precipitated by metabolic stress circumstances like infection ( 6, 7), persists despite chronic dietary treatment adherence. Treatment for severe forms may involve liver transplantation to replace functional branched-chain α-ketoacid dehydrogenase complex in the liver. The standard therapeutic approach includes BCAA restriction by natural dietary protein limitation and supplementation of BCAA-free formula. The increase of αKIC in tissues explains the inverse relationship of leucine to glutamate, glutamine, and alanine in classical MSUD patients as it reverses normal flow through branched-chain amino acid transaminase (BCAT1), depletes tissues of glutamate and indirectly drives flux through glutamate-pyruvate transaminase ( 5). Both act as metabolic inhibitors and αKIC, which enters the brain via the monocarboxylate transporter (SLC16A1), also act as an uncoupler of oxidative phosphorylation ( 4). Leucine and KIC are considered the main neurotoxins in this disorder. In the pathogenesis of neurological damage in MSUD, an increasingly role of the neurotoxic properties of the BCAA and BCKA is recognized ( 1), disturbing brain bioenergetics and redox homeostasis ( 2), inducing neuroinflammation ( 3) and contributing to a reduction of brain glutamate, glutamine, and gamma-aminobutyrate concentrations ( 4). The elevated blood level of BCAAs impairs cerebral uptake of large neutral amino acids thought the blood-brain barrier, decreasing their concentration in brain ( 1). Maple syrup urine disease (MSUD, OMIM 248600) is a rare inborn metabolic disorder involving a deficiency of the branched chain α-ketoacid dehydrogenase complex that results in tissue accumulation of the branched-chain amino acids (BCAAs) and their respective branched-chain α-keto acids (BCKA): α-ketoisocaproic (αKIC), α-ketoisovaleric and α-keto-β-methylvaleric acids. No related adverse events were observed.Ĭonclusions: Administration of standardized IV BCAA-free solution in emergency settings constitutes an important and safe alternative for the treatment of DEs in MSUD, especially in pediatric patients for whom oral or enteral treatment is not viable. Administration of IV BCAA-free solution at the beginning of a DE could reverse depletion of the amino acids that compete with BCAAs for the LAT1 transporter, and the observed depletion of alanine, despite IV alanine supplementation. The duration of administration ranged from 3–20 days. Leucine normalization was achieved in all cases with resolution or improvement of clinical symptoms following IV BCAA-free solution. Results: We evaluated the use of BCAA-free solution in 5 DEs in 5 MSUD pediatric patients, all with significantly elevated plasma leucine levels at admission (699–3296 μmol/L) and in 1 episode of risk of DE due to surgery. Clinical evolution, amino acid profile and adverse effects were evaluated. Methods: This pediatric series discusses the management of DEs in MSUD patients with IV BCAA-free solution, as an emergency treatment for DEs or as a prophylactic in cases requiring surgery. Intravenous (IV) administration of BCAA-free solution could represent a powerful alternative for emergency treatment of decompensations. These episodes require immediate intervention to prevent irreversible neurological damage.
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