What are metabolic disorders?
Metabolic disorders are genetic diseases that interfere with the body's ability to process specific substances. Often, the body is missing an enzyme that is needed to process a certain type of amino acid. As a result, these acids can build up in the body causing health problems.
Many metabolic disorders need special dietary therapy. Dietary therapy is a way of limiting the intake of the substance the body does not process well by avoiding certain foods and eating a special diet. People with metabolic disorders need ongoing counseling and monitoring by a team of physicians, nurses, genetic counselors, social workers, and dietitians for improved health and longevity.
PKU and MSUD
Two common diet-affected metabolic disorders are PKU or phenylketonuria, and Maple Syrup Urine Disease (MSUD). Both conditions involve deficiency in an enzyme that breaks down an amino acid into another compound. This means that the essential amino acid tends to build up in the body, causing problems.
Phenylketonuria (PKU)
PKU is a complete absence or deficiency in phenylalanine hydroxylase (PAH), an enzyme involved in metabolizing or converting the amino acid phenylalanine into tyrosine, another amino acid. PAH deficiency results in high levels of blood phenylalanine and an accumulation of phenylketones in the urine.
Partial deficiency of the enzyme results in hyperphenylalaninemia. In this condition, the child has elevated blood phenylalanine, although it is not quite as high as when there is a complete absence of PAH. In hyperphenylalaninemia, phenylketones do not accumulate.
Unless it is recognized and treated soon after birth, PKU will cause brain damage.
In the United States, PKU is most common in white and Native Americans and less common in African American, Hispanic, and Asian.
Maple Syrup Urine Disease (MSUD)
Maple Syrup Urine Disease (MSUD) is a disorder in the body’s ability to use three so called branched-chain amino acids (BCAAs): leucine, isoleucine, and valine.
In MSUD, the enzymes needed to break down leucine, isoleucine, and valine are either absent, inactive, or only partially active. As a result, the BCAAs and their by-products, called ketoacids, become elevated in the blood. If untreated, this results in an altered mental state and brain damage.
MSUD gets its name from the sweet, burnt sugar or maple syrup smell of the urine. Early diagnosis and a special diet can prevent complications and allow for normal intellectual development.
MSUD is very rare.
Special diets for PKU and MSUD
For the most severe form of PKU, high-protein foods are removed from the diet, since all protein contains phenylalanine. This means that all concentrated sources of protein must be eliminated from the diet in order to limit the amount of phenylalanine.
Similarly, long-term treatment of MSUD involves a carefully controlled diet that strictly limits dietary protein in order to prevent the accumulation of BCAAs in the blood. Except in rare circumstances, the diets for these conditions do not allow consumption of meat, fish, poultry, milk, eggs, cheese, ice cream, legumes, nuts, or many products containing regular flour.
People with PKU or MSUD must drink special medical formulas, synthetically made as a nutritional substitute for the eliminated foods. The PKU formula does not contain any phenylalanine, and the MSUD formula does not contain any leucine, isoleucine, or valine. Otherwise, these formulas are nutritionally complete. They contain all the necessary vitamins, minerals, and other essential amino acids needed for normal growth and development.
Because phenylalanine, leucine, isoleucine, and valine are essential amino acids, people with these disorders do require small amounts of them. Thus, the special diets are supplemented with low-protein foods and weighed or measured amounts of fruits, vegetables, and some grain products. These types of foods contain lower amounts of protein, but provide the necessary amount of essential amino acid(s) based on the patient’s specific need. These foods must be carefully measured or weighed, as the quantity of the "problem" amino acid(s) allowed in the patient’s diet is based on their individual tolerance. Some children can have fairly liberal diets and still maintain good control of blood amino acid levels. Others must follow a very strict diet.
Maintaining the special diet
In the early days of treating PKU, it was believed that the diet could be stopped at an early age. However, it is now known that stopping the diet can result in a variety of serious problems, including lowering in IQ, learning disabilities, behavioural problems such as hyperactivity and irritability, neurological problems such as tremors, eczema, and personality disorders including schizophrenia, panic attacks, and agoraphobia.
All PKU patients should follow their prescribed diet for life.
Similarly, for MSUD, experts strongly agree that following the diet for life is the best therapy for an optimal outcome.
Minor illness and infection: now very serious
Any common illness or infection can cause a rise in phenylalanine or BCAAs. This may result in an episode of vomiting, diarrhea, irritability, sleepiness, unusual breathing, staggering, hallucinations, and slurred speech. If left untreated, the child can go into a coma and die. Therefore, at any sign of illness parents should contact a health care provider to begin treatment for the illness. Parents may also begin an illness management protocol or sick day plan.
The illness management protocol is designed to keep a child out of the hospital. It is a plan that provides enough calories and amino acids to meet the body's needs and to use up the excess phenylalanine or BCAAs in the blood by promoting protein synthesis. Usually the "sick day diet" lowers phenylalanine or leucine intake and increases the amount of formula the child is prescribed. Blood tests may be more frequent at these times to check amino acid levels.
PKU and MSUD in the long term
Without prompt treatment, the build up of phenylalanine or BCAA in the blood results in progressive brain damage. This is most important during the early months of life when there is very rapid brain growth.
Research being done across the world has shown that if a diagnosis is made and treatment is started in the first few weeks of life, normal brain development is not disturbed or affected. Therapy of a strict diet and the right medical care must be started at the earliest possible age to achieve the best outcome.
Metabolic disorders and genetics
PKU and MSUD are inherited recessive genetic diseases. This means both parents of a child with PKU or MSUD must carry a mutation in the same gene. These mutated genes do not function normally, thus causing disease.
Each individual person has two genes that code for the enzyme activity involved in the breakdown of an amino acid—one gene coming from the father and one from the mother. If one gene functions normally, but the other does not, then the person is a carrier of PKU or MSUD. If neither gene functions normally, then that person has PKU or MSUD. It is also possible to receive the normal gene from each parent and not have any mutated genes for the disease.
Ask to speak with a genetic councelor about your family's situation.
Key Points
- Metabolic diseases, specifically PKU and MSUD, are serious disorders that are life-threatening unless addressed promptly.
- Careful monitoring and adherence to dietary restrictions are essential.
- Minor illnesses and infections must be taken seriously and require special care.
- When a strict diet is initiated early and maintained well, affected children can expect normal development and a normal life span.
This article was written by the registered dietitians at the Specialty Food Shop at The Hospital for Sick Children.