Provide aggressive nutrition management during illness or at first presentation to prevent or reverse catabolism and promote anabolism by supplying: adequate energy (up to 150% of usual energy intake); BCAA-free protein (increased to replace BCAA-containing intact protein); fluid (up to 150ml/kg with careful monitoring of electrolytes and possible cerebral edema); and electrolytes and insulin (if needed).

Use parenteral nutrition alone (providing BCAA-free amino acids, lipids and/or glucose) or in conjunction with enteral feedings, when necessary to meet energy needs in severe illness.

Monitor BCAA, acid-base balance, urine α-ketoacids, blood glucose and clinical symptoms closely during illness. If hemofiltration is necessary, blood gas, hematocrit, total protein, sodium, calcium, phosphorus, urea, and creatinine should also be monitored.

Include nutritional intervention when dialysis, hemofiltration or similar treatment is necessary to lower plasma BCAA and remove toxic metabolites.

Add ILE and VAL, even if plasma concentrations are already in the 200-400 µmol/L range, to help lower elevated plasma LEU into the treatment range.

Reintroduce intact protein (or complete amino acid mixtures) when elevated plasma LEU approaches the upper limit of the treatment range: 200 µmol/L for infants and children ≤ 5 years of age and 300 µmol/L for individuals > 5 years of age.

Consider use of breast milk (mean LEU concentration of 1 mg/mL) as a source of intact protein (and BCAA) in the dietary management of infants with MSUD if there is frequent anthropometric, clinical, and laboratory monitoring of the infant, and mother has adequate milk production. See TABLE #6, Recommendations for the Nutritional Monitoring of Individuals with MSUD.

Manage mild illnesses with patient-specific sick-day instructions to include: reduction of intact PRO by 50-100% for 24-48 hours by replacement with additional BCAA-free medical food; adequate hydration; addition of non-protein energy sources; and close monitoring.