Inflammation in maple syrup urine disease.

Maple syrup urine disease (MSUD), also called leucinosis, is a rare inborn error of metabolism characterized by the deficiency of an enzyme complex: branched-chain alpha-keto acid dehydrogenase (BCKAD). This complex is located in the mitochondria and is responsible for metabolizing the three essential branched-chain amino acids (BCAA): isoleucine, leucine, and valine. As the patient with MSUD cannot directly break down these "building blocks" of protein, a harmful build-up of substances in the plasma, urine and tissues will follow. In this review, we overview available data of inflammation in MSUD patients, cells and animals and discuss possible pathophysiological links. Available studies demonstrate that exposure to high levels of BCAAs leads to altered expression of inflammatory markers in cells, animals, and patients with MSUD. Proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ are commonly elevated in specific brain regions, while anti-inflammatory responses (e.g., IL-10) may be suppressed. Additionally, increased expression of cell adhesion molecules (sICAM-1, sVCAM-1) and receptor for advanced glycation end-products (RAGE) has been observed. These findings suggest that inflammation may play an important role in MSUD pathophysiology. Further studies are needed to clarify the relationship between inflammatory imbalance, neurodegeneration, and clinical outcomes in MSUD.