Maple Syrup Urine Disease (MSUD) is an autosomal recessive metabolic disorder caused by deficient activity of the branched-chain 2- ketoacid dehydrogenase enzyme complex. Delay in starting treatment and inadequate treatment at times of increased metabolic stress results in severe, sometimes fatal, neurological deterioration.

The branched-chain 2-ketoacid dehydrogenase enzyme complex is responsible for the metabolism of the three branched-chain amino acids (BCAA's): leucine, isoleucine and valine. Deficiency of the enzyme complex therefore leads to an accumulation of these three amino acids and their respective ketoacids in plasma and urine.

MSUD can be classified clinically into three types:

1. Classical MSUD - the most severe and common form, presenting at 4 - 6 days of life. If not treated promptly by diet there is a rapid progression from poor feeding and lethargy to neurological deterioration, coma and death.

2. Intermediate MSUD - patients are well, with BCAA concentrations near normal except at times of metabolic stress such as intercurrent infections.

3. Thiamine responsive MSUD - less severe than other variant disorders. Requires less severe dietary restriction and symptoms may respond to pharmacological doses of thiamine.

DIETARY TREATMENT

Early diagnosis, combined with good long term metabolic control is essential in minimizing neurological impairment and poor intellectual development in MSUD. Leucine is considered to be the most toxic of the BCAA's and it is present in food in greater concentration than isoleucine or valine. The diet is therefore based on restriction of the leucine intake.

Essential components of diet:

• Leucine - is an essential amino acid and cannot be excluded from the regular dietary regimen of patients with MSUD. It must be restricted according to individual tolerance and measured using an exchange system of either 50 mg Leucine exchanges, ½ g protein exchanges or 1g protein exchanges
• Protein Substitute - providing BCAA-free amino acids
• A comprehensive vitamin, mineral and trace element supplement
• Isoleucine and Valine Amino Acid Supplements - although the plasma concentration of these two amino acids is usually above the normal reference range there are occasions isoleucine and/or valine fall below the target, or if it appears to be disproportionately low compared to the leucine, a supplement is essential. If it is not provided the low isoleucine and/or valine will become rate limiting for protein synthesis with a consequent deterioration in metabolic control
• Energy - sufficient energy must be provided from (1) foods naturally low in or free from protein (2) specially manufactured low protein foods (3) protein-free energy supplements in the form of glucose polymers and fat emulsions in order to maintain appropriate weight and prevent catabolism.

Conventional protein substitutes are high volume drinks or nutritionally incomplete products which require further supplementation with micronutrients. These can be inconvenient and lead to poor compliance and poor metabolic control.

Vitaflo have developed a range of products to fulfill the needs of patients with MSUD.

MSUD gel (1-10years)

MSUD express (8 years +)

MSUD express cooler (8 years +)

Isoleucine Amino Acid Supplement (all ages)

Valine Amino Acid Supplement (all ages)

MSUD gel and MSUD express have been specifically designed as low volume, nutritionally complete protein substitutes setting a new standard of acceptance and convenience in this category of products.

Isoleucine Amino Acid Supplement and Valine Amino Acid Supplement are welcome additions to the range fulfilling a previously unmet need for dose related supplements of these amino acids in a form that can be quickly and easily incorporated into the diet when required.