Application of Swietenia macrophylla Polymer/Nanocomposites for Mitigating Paraffin Wax Deposition.

Maple syrup urine disease (MSUD) is a rare, autosomal recessive, inherited disorder, caused by biallelic mutations in the , , , or genes []. The estimated incidence of MSUD is 1 per 185,000 live births worldwide [], 2 per 201,000 in Italy [], 1 per 200,000 in the United States (US) [], 1 in 147,975 in Ireland [], and 3 in 626,000 in France []. Similar to other metabolic conditions, MSUD is detected either through clinical presentation or newborn screening (NBS); NBS of MSUD relies on the detection of specific amino acids (AAs; leucine, isoleucine, or valine), which are known collectively as branched-chain AAs (BCAAs) []. In contrast to classic organic acidurias, such as propionic and methylmalonic acidemias, which are mainly caused by accumulation of organic acids and subsequent mitochondrial toxicity [], MSUD is caused by a deficiency of branched-chain ketoacid dehydrogenase (BCKD), the enzyme necessary for the second step in the catabolism of the three branched-chain ketoacids derived from the BCAAs [, ]. BCKD deficiency leads to elevated circulating plasma levels of all three BCAAs, which have specific neurotoxicity. Leucine is present at the highest levels [], with lesser, but still substantial, accumulation of valine and isoleucine []. Alloisoleucine is a sensitive, specific, and reliable diagnostic marker of all forms of MSUD; this derivative of isoleucine is almost undetectable under normal physiological conditions. Diagnostic confirmation of MSUD is achieved with testing of the ,, and genes []. Acute metabolic decompensation (AMD) in MSUD is caused by the accumulation of BCAAs, especially leucine, usually triggered by excess protein intake or endogenous protein catabolism because of infection, surgery, injury, fasting, or a significant dietary change [, ]. Guidelines for management of AMD in patients with MSUD recommend monitoring of BCAA levels, cessation of protein intake, administration of carbohydrate- and fat-based calories, maintaining hydration, preventing dilutional electrolyte imbalance by avoiding hypo-osmolar solutions, up titration of BCAA-free feeds (referred to henceforth as BCAA-free solutions or mixtures) and, if necessary, dialysis [, –]. As therapy continues, isoleucine and valine levels decrease, leading to a deficiency of these BCAAs; therefore, patients require isoleucine and valine supplementation. Care should be taken to avoid excessive fluid administration, to minimize the risk of hyponatremia and subsequent brain edema.