Your disease

Biochemical overview

Your child has a disorder known as Maple Syrup Urine Disease (MSUD). Your training at the hospital has just taught you that proteins are catabolised into amino acids in the gastrointestinal tract.

Individuals with maple syrup urine disease are unable to further break down three amino acids known as branched-chain amino acids: leucine, valine and isoleuicne. The cause of this disorder is a deficiency of the enzyme responsible for the second stage of the metabolism of these three amino acids.

This enzyme is common to the catabolism of these three amino acids. As a result, these three ketoacids and their corresponding amino acids accumulate in blood, urine and body tissues, leading to progressive toxicity (mainly due to leucine) that requires prompt treatment, particularly in acute-onset forms.

The prevalence of this disease is approximately 1/200,000 births.

Maple syrup urine disease usually presents within the first few days of life (neonatal acute form), but some rare forms present later (progressive toxicity) or are intermittent. In exceptional cases, certain forms may respond to treatment with thiamine (vitamin B1).

 


Your treatment

Fig. 7: Diagram of the metabolism of branched-chain amino acids

The mainstay of treatment for maple syrup urine disease is a diet with carefully controlled levels of these three amino acids, which clears these toxic substances from the body and limits their formation in order to bring their blood concentration close to normal levels.

Achieving this balance prevents acute episodes and/or neurological complications. The treatment must be continued for life. Your child therefore needs to follow a special diet, which should start as soon as possible and meet all the requirements of the child. It is CRUCIAL to learn how to manage and follow your child’s diet.

Leucine, valine and isoleucine are “essential amino acids”, which means they cannot be made by the body. As a result, they must come from food to meet the individual’s growth and protein turnover requirements.

The principles of treatment are set out in the first part of the guide (“common core”) and are based on:

  • natural foods that provide the amounts of leucine, valine and isoleucine your child needs;
  • a mixture of amino acids that covers the requirements for other essential amino acids; and
  • hypoproteic foods that aim to round out the child’s energy intake with sugars and fats.

 

Natural foods: a how-to guide

All protein-containing foods have leucine, valine and isoleucine in varying proportions. Together, these three amino acids make up 25% of animal protein and 10 to 15% of plant protein. Leucine is the most common amino acid (10% of animal protein and 5 to 7% of plant protein on average), as well as the one with the greatest toxic effects in high concentrations.

As a result, the diet will be calculated based on leucine intake, which will also limit the intake of valine and isoleucine. Foods must be chosen and given in set amounts tailored to each child’s specific case.

There are three types of foods:

Forbidden foods

Because their leucine, valine and isoleucine content is too high (see the list of forbidden foods provided by your healthcare centre)

For perspective, and to help you understand why these foods are forbidden, here are two examples:

  • one yoghurt contains over 500 mg of leucine, while individuals with the most severe forms of this disorder (neonatal forms) can generally tolerate no more than 300 to 350 mg of leucine a day!
  • Another example: Half a baguette of bread contains 800 mg of leucine, which is more than twice the recommended daily allowance set in the previous example!

Controlled foods

Because they contain lower amounts of leucine, valine and isoleucine and help to provide the recommended allowances of these amino acids. They must be given in moderate amounts and weighed.

Intake is calculated based on their leucine content. In the immediate post-neonatal setting, the amount of leucine (and, therefore, valine and isoleucine) comes from a controlled amount of infant milk formula. From the time of diversification (which takes place at a normal age, ranging from 4 to 6 months depending on each specific case), leucine will come from fresh, canned or deep-frozen fruits and vegetables.

Lists of fruits and vegetables with known composition have been compiled, including their equivalence in parts of leucine. A part of leucine is defined as 50 mg of this amino acid. The lists of foods set out the amount (weight or volume) of each food that contains 1 part of leucine (50 mg). These lists will help you to calculate the diet of your child by controlling the leucine content of each meal. At the time of diversification, you will learn the composition of foods and “choose” from the list to cover your child’s recommended leucine intake and sate your child’s appetite. A consensus has been reached on these reference tables, but each centre can have its own system.

Permitted foods

Because they are poor in protein: all fats and sugars.

This controlled intake of natural foods helps to tailor the amounts of leucine, isoleucine and valine to the tolerance of your child. Tolerance is the amount of amino acids that meets growth and protein turnover requirements without overshooting the body’s ability to eliminate excess amounts of these amino acids. 

 

Each child can have a different degree of tolerance (within a narrow range), so the diet may vary from one child with maple syrup urine disease to another. Your child’s tolerance will be tested during the first few months and change very little thereafter.

 

Prescription of amino acids mixes

A controlled intake of natural foods helps to limit the intake of leucine, isoleucine and valine, but it also restricts the intake of other essential amino acids, which do not cause toxicity in individuals with maple syrup urine disease but are necessary for your child to grow and develop properly.

It is therefore necessary to round out your child’s intake of these other essential amino acids to prevent deficiencies. This is done by prescribing a amino acids mixes that contains all essential amino acids except for the three toxic ones. This amino acids mixes must be taken every day in the prescribed quantities and in several doses during the day.

There is a wide range of amino acids mixes with different compositions (higher or lower energy content), tailored to every age, with different textures, packaging and flavours (e.g. powders, gels, liquids, in boxes, in sachets, in flasks, with natural flavours, vanilla, fruits, etc.). You may find the flavour or smell of these mixtures peculiar or even unpleasant, but rest assured that your child will soon get used to them, especially if you start giving these mixtures within the first few days after birth, turning it into part of your child’s “normal” foods.

The choice of mixture should be based on your child’s appetite and, later on, taste preferences. The prescribed amounts will meet your child’s requirements for essential amino acids other than leucine, isoleucine and valine. These essential amino acid supplements also contain minerals, vitamins and trace elements, which cover the child’s needs at every age. They provide energy in the shape of a variable amount of fat and sugar.

Infants grow very quickly, so their nutritional requirements are high. The amounts of mixture given will be adjusted regularly.

Dietary changes will also take into account the intake of the three controlled amino acids (tolerance) and the balance of plasma levels in your child, as well as the child’s appetite, growth and health status.

NOTE: Your child may also get a prescription for valine and/or isoleucine capsules. Their aim is to prevent a deficiency of one of these two amino acids. As explained earlier (see “Natural foods”), a controlled intake of leucine implies a restricted intake of valine and isoleucine, which can sometimes be too low and lead to a secondary deficiency of these two amino acids. Such a deficiency is usually detected by blood tests. It can be treated with oral supplementation of these two amino acids.

Not all children need to take these supplements!

 

Low protein foods

The diet described above is enough to meet essential amino acid requirements, but it often fails to provide enough calories. As a result, more energy needs to be provided in the shape of fats and sugars in low protein foods. In the first few months, amino acids mixes (a “diet milk” of sorts) generally contains enough calories from fats and sugars.

“Low protein” foods should be gradually introduced during diversification to round out the child’s energy intake. The variety, appearance and packaging of these low protein foods also help to create menus similar to those of a normal diet. These products can be eaten at will because they contain no “toxic” amino acids.