Isoleucine

Maple syrup urine disease (MSUD)^1,2

MSUD is an inherited metabolic disorder caused by branched-chain α-ketoacid dehydrogenase (BCKD) deficiency, resulting in the accumulation of branched chain amino acids (BCAAs) L-leucine, L-isoleucine and L-valine. MSUD varies considerably in disease severity, with clinical features including seizures, ketoacidosis, hypoglycaemia, apnoea, ataxia and coma.

Elevated L-leucine levels are toxic and associated with abnormal brain morphology and cognitive impairment. This may impact on social and psychomotor function. The mainstay of dietary management is the restriction of dietary BCAAs, especially L-leucine, and the use of BCAA-free protein substitutes (PS).

To promote anabolism of L-leucine, when L-leucine blood concentrations are high, additional supplementation with L-isoleucine may be required. In addition, patients on dietary management can develop an L-isoleucine deficiency, which is absent from their PS. This can lead to a rash and can also involve the eye and gut epithelium. Supplementation of the diet with L-isoleucine supplements is used to manage this.