Nutrition therapy plays an essential role in stabilizing and restoring metabolic homeostasis in MSUD. At diagnosis or any time there is a risk of metabolic decompensation during trauma, illness, dietary non-compliance or surgery, the goals are to: closely monitor biochemical and clinical status; prevent catabolism and the accumulation of endogenous BCAA and BCKA; and provide adequate BCAA-free exogenous protein, energy, fluid, and VAL and ILE to promote anabolism. When the patient is metabolically stable, LEU requirements can be met from intact protein sources. Seriously ill individuals need aggressive treatment that may include dialysis, parenteral nutrition and/or tube feedings. Non-acutely ill individuals can often be managed with a “sick day” guideline that provides instruction for preventing catabolism and monitoring clinical status.
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).
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |
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.
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |
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.
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |
Include nutritional intervention when dialysis, hemoperfusion or similar treatment is necessary to lower plasma BCAA and remove toxic metabolites.
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |
Add ILE and VAL, even if they are already in the 200-400 µmol/L range, to help lower elevated plasma LEU into the treatment range.
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |
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.
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |
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 #7, Recommendations for the Nutritional Monitoring of Individuals with MSUD.
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |
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.
Insufficient Evidence | Consensus | Weak | Fair | Strong |
Conditional | Imperative |