Diet principles - MSUD

The main goals of nutritional management in MSUD are to stabilize and restore metabolic homeostasis by rapidly reducing toxic metabolites restricting BCAA to amounts that achieve target plasma BCAA levels.

LEU, VAL and ILE are essential amino acids, which cannot be synthesized by the body, and thus needs to be obtained from a food source. The amount of LEU, VAL, ILE the diet is needed for optimal growth and development, but restricted to the level allowed to prevent excessive build-up in the blood, depending on the residual BCKD activity, growth velocity.

During illness, catabolism increases endogenous production of BCAA which requires aggressive nutritional management at first presentation to prevent a metabolic crisis, to reverse catabolism and promote anabolism. Each patient should be provided with a personal emergency plan to manage acute or non-acute illness.

The diet for MSUD patients must be individualized depending on each patient’s nutrient and growth needs. Close monitoring is essential.¹

Diet principles^1,2

Aim for normalizing plasma amino acids levels of the BCAAs: LEU, VAL, ILE. Limit the intake of dietary of BCAAs by restricting the natural protein intake to maintain blood levels within in the desired range
Ensure sufficient intake of LEU is required for adequate protein synthesis to allow optimal growth and repair and to achieve adequate LEU levels. LEU allowance is dependent on the residual BCKD activity, age weight and life stage. Since the tolerance for LEU is lower than for VAL and ILE, the target levels for LEU may not be met, so supplementation is required
Ensuring an adequate amount of dietary BCAAs by natural protein intake, to support normal growth and development but also to maintain blood BCAA levels within the desired range. Total protein recommendations are based on recommendations for the healthy population + 20% for amino acid based supplementation
Adequate amino acid supplementation by a BCAAs free L-amino acid supplement, micronutrients, essential fatty acids (EFA) and long chain polyunsaturated fatty acids (LCPUFAs) up to a level recommended in the age range, in order to maintain adequate protein status for MSUD patients
Adequate energy intake to promote appropriate growth and weight maintenance and prevent catabolism
Supplementation of thiamin in case of thiamin responsiveness
Monitor nutritional status and adjust diet as needed
Provision of a palatable, varied and ‘easy to maintain’ diet
Provision of an emergency regimen during illness, fasting and infections, surgery or increased activity.

MSUD types requiring dietary management¹
Type	Age of onset	Clinical symptoms	Dietary management
Classical form less than 3% of normal enzyme activity	Neonatal onset	Symptoms can occur soon after birth. Poor feeding, lethargy, ketoacidosis, seizures	Low BCAA diet Low LEU tolerance Requires emergency regimen
Intermediate 3-30% of normal enzyme activity	Presents at any age	Failure to thrive, ketoacidosis and developmental delay	Low BCAA diet Requires emergency regimen
Intermittent 5-20% of normal enzyme activity	Infancy to adults	Normal early development, episodic ataxia/ketoacidosis	Generally tolerate normal to moderate restriction of LEU intake when well. Requires emergency regimen
Thiamin responsive 2-40% of normal enzyme activity	Late onset	Similar to intermediate	Requires dietary restriction but less severe than classic MSUD Requires emergency regimen

Standard nutritional management for patients with MSUD^2,3,4
Mg/kg/day	Neonates	Infants	Young children	Older children and adults
Leucine tolerance	40-100	35-75	20-65	5-50
Valine intake	40-95	30-80	20-50	15-50
Isoleucine intake	30-90	20-70	10-30	5-30

References

Dixon MD, MacDonald A, White F, Stafford J. In: Clinical Paediatric Dietetics. 4^th ed: West Sussex: John Wiley & Sons Limited, 2014:381-525.
GMDI: Nutrition Management guidelines for MSUD. https://southeastgenetics.org/ngp/guidelines.php
Calcar van S. Nutrition Management of Maple Syrup Urine Disease. In: Bernstein L.E. et al (eds), Nutrition Management of Inherited Metabolic Diseases, Springer International Publishing Switzerland 2015