Children and Youth with Special Health Needs (CYSHN)

Trifunctional Protein Deficiency (TFP)

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Condition Information

Treatment Options: Taking Action

Family Support Resources

CONDITION INFORMATION

TFP deficiency stands for “trifunctional protein deficiency”. It is one type of fatty acid oxidation disorder. Some people with TFP deficiency have problems breaking down fat into energy for the body.

What is TFP deficiency?

TFP deficiency stands for “trifunctional protein deficiency”. It is one type of fatty acid oxidation disorder. Some people with TFP deficiency have problems breaking down fat into energy for the body.

Fatty Acid Oxidation Disorders:

Fatty acid oxidation disorders (FAODs) are a group of rare inherited conditions. They are caused by enzymes that do not work properly.

A number of enzymes are needed to break down fats in the body (a process called fatty acid oxidation). Problems with any of these enzymes can cause a fatty acid oxidation disorder. People with FAODs cannot properly break down fat from either the food they eat or from fat stored in their bodies.

The symptoms and treatment vary between different FAODs. They can also vary from person to person with the same FAOD. See the fact sheets for each specific FAOD.

FAODs are inherited in an autosomal recessive manner and affect both males and females.

What causes TFP deficiency?

TFP deficiency occurs when a group of enzymes, called “trifunctional protein” (TFP), is either missing or not working properly. The job of TFP is to break down certain fats from the food we eat into energy. It also breaks down fat already stored in the body

Trifunctional Protein (TFP) Deficiency chart

Energy from fat keeps us going whenever our bodies run low of their main source of energy, a type of sugar called glucose. Our bodies rely on fat when we don't eat for a stretch of time - like when we miss a meal or when we sleep. Our bodies rely on fat when we don‟t eat for a stretch of time – like when we miss a meal or when we sleep.

When TFP is missing or not working well, the body cannot use fats for energy. Instead, it must rely solely on glucose. Although glucose is a good source of energy, there is a limited amount available. Once the glucose has been used up, the body tries to use fat without success. This leads to low blood sugar, called hypoglycemia, and to the build up of harmful substances in the blood.

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What causes the TFP enzyme to be absent or not working correctly?

Genes tell the body to make various enzymes. People with TFP deficiency have a pair of genes that do not work correctly. Because of the changes in this pair of genes, the TFP enzyme either does not work properly or is not made at all.

How is TFP deficiency inherited?

TFP deficiency is inherited in an autosomal recessive manner. It affects both boys and girls equally.

Everyone has a pair of genes that make the TFP enzyme. In children with TFP deficiency, neither of these genes works correctly. These children inherit one non-working gene for the condition from each parent.

Parents of children with TFP deficiency rarely have the disorder. Instead, each parent has a single non-working gene for TFP deficiency. They are called carriers. Carriers do not have the condition because the other gene of this pair is working correctly.

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have TFP deficiency. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.

Autosomal Recessive Inheritance chart

Genetic counseling is available to families who have children with TFP deficiency. Genetic counselors can answer your questions about how the condition is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselor.

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Is there genetic testing available?

Genetic testing for TFP deficiency can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes in the pair of genes that cause the condition. In some affected children, both gene changes can be found. However, in other children, neither or only one of the two gene changes can be found, even though we know they are present.

DNA testing is not necessary to diagnose your child. It can be helpful for carrier testing or prenatal diagnosis, discussed below. Ask your metabolic doctor or genetic counselor if you have questions about DNA testing for TFP deficiency.

What other testing is available?

TFP deficiency can be confirmed by special enzyme tests using a skin or muscle sample. Your doctor or genetic counselor can answer your questions about testing for TFP deficiency.

Can you test during pregnancy?

If both gene changes have been found in the child with TFP deficiency, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or amniocentesis. CVS stands for Chorionic Villus Sampling, which is a special test done early in pregnancy. During CVS, a small sample of the placenta is removed for genetic testing.

If DNA testing would not be helpful, special enzyme tests can be done during pregnancy using cells from the fetus. Again, the sample needed for this test is obtained by either CVS or amniocentesis

Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.

Can other members of the family have TFP deficiency or be carriers?

Having TFP deficiency
The brothers and sisters of a baby with TFP deficiency have a chance of being affected even if they haven't had symptoms. Finding out whether other children in the family have this condition is important because early treatment may prevent serious health problems. Talk to your doctor or genetic counselor about testing your other children for TFP deficiency.

TFP deficiency carriers
Brothers and sisters who do not have TFP deficiency still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done in people over 18 years of age.

Each of the parents' brothers and sisters has a 50% chance to be a carrier. It is important for other family members to be told that they could be carriers. There is a small chance they are also at risk to have children with TFP deficiency.

When both parents are carriers for TFP deficiency, newborn screening results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done

During pregnancy, women carrying fetuses with TFP may be at increased risk to develop serious medical problems. There is a small risk of:

  • excessive vomiting
  • abdominal pain
  • high blood pressure
  • jaundice
  • abnormal fat storage in the liver
  • severe bleeding

All women with a family history of TFP should share this information with their obstetricians and other health care providers before and during any future pregnancies. Knowing about these risks allows better medical care and early treatment if needed.

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Can other family members be tested?

Diagnostic testing for TFP deficiency
Brothers and sisters of an affected child can be tested for TFP deficiency using either DNA testing or special enzyme tests.

Carrier testing for TFP deficiency
If both gene changes have been found in the child with TFP deficiency, other family members can have DNA testing to see if they are carriers.

How many people have TFP deficiency?

TFP deficiency is very rare. The actual incidence is unknown.

Does TFP deficiency happen more frequently in a certain ethnic group?

TFP deficiency does not happen more often in any specific race, ethnic group, geographical area or country.

Does TFP deficiency go by any other names?

TFP deficiency is sometimes also called:

  • mitochondrial trifunctional protein deficiency

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TREATMENT OPTIONS: TAKING ACTION

What is the treatment for TFP deficiency?

Your baby's primary doctor may work with a metabolic doctor and a dietician to care for your child.

Certain treatments may be advised for some children but not others.  When necessary, treatment is usually needed throughout life.  The following are treatments that may be recommended for children with this condition:

1.

Avoid going a long time without food
Infants and young children with TFP deficiency need to eat frequently to prevent hypoglycemia or a metabolic crisis. Your metabolic doctor will tell you how often your child needs to be fed.  In general, it is often suggested that infants be fed every four to six hours. Some babies need to eat even more frequently than this. It is important that infants be fed during the night. They may need to be woken up to eat if they do not wake up on their own. Your metabolic doctor and dietician will give you an appropriate feeding plan for your infant. Your doctor will also give you a ‘sick day’ plan tailored to your child’s needs for you to follow during illnesses or other times when your child will not eat.

Your metabolic doctor will continue to advise you on how often your child should eat as he or she gets older.  When they are well, many teens and adults with TFP deficiency can go without food for up to 12 hours without problems. The other treatments usually need to be continued throughout life. 

2.

Diet
A low fat, high carbohydrate food plan is often recommended. Carbohydrates give the body many types of sugar that can be used as energy. In fact, for children needing this treatment,most food in the diet should be carbohydrates (bread, pasta, fruit, vegetables, etc.) and protein (lean meat and low-fat dairy foods). Any diet changes should be made under the guidance of an experienced dietician. 

People with TFP deficiency cannot use certain building blocks of fat called “long chain fatty acids”. Your dietician can help create a food plan low in these fats. Much of the rest of the fat in the diet will likely be in the form of medium chain fatty acids. 

Ask your doctor if your child needs to have any changes in his or her diet.  
3.

MCT oil and L-carnitine
Medium Chain Triglyceride oil (MCT oil) is often used as part of the food plan for people with TFP deficiency. This special oil has medium chain fatty acids that can be used in small amounts for energy. Your metabolic doctor or dietician can tell you how to use this supplement. You will need to get a prescription from your doctor to get MCT oil. 

Some children may be helped by L-carnitine. This is a safe and natural substance that helps body cells create energy. It also helps the body get rid of harmful wastes. Your doctor will decide whether your child needs L-carnitine.  Unless you are advised otherwise, use only L-carnitine prescribed by your doctor.

Do not use any medication or supplement without checking with your doctor.
4.

Call your doctor at the start of any illness:
Always call your doctor when your child has any of the following:

  • poor appetite
  • low energy or excessive sleepiness
  • vomiting
  • diarrhea
  • an infection
  • a fever
  • persistent muscle pain or weakness
  • reddish-brown color to the urine

Children with TFP deficiency need to eat extra starchy food and drink more fluids during any illness - even if they may not feel hungry - or they could develop a metabolic crisis. Children who are sick often don’t want to eat. If they won’t or can’t eat, children with TFP deficiency may need to be treated in the hospital to prevent hypoglycemia or metabolic crisis. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.
5.

Avoid heavy exercise and extreme cold.
Long periods of heavy exercise can trigger symptoms in people with TFP deficiency. Effects of exercise can include muscle aches, cramps and weakness. Muscle fibers may break down. This can turn the urine a reddish-brown color.

If muscle symptoms occur, prompt treatment is needed to prevent kidney damage. Children or adults with muscle symptoms should:

  • drink fluids right away
  • eat something starchy or sugary
  • get to a hospital for treatment.

To prevent muscle symptoms:

  • avoid prolonged or heavy exercise
  • avoid extreme cold
  • eat starchy or sugary foods before and during periods of moderate exercise or exertion

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What happens when TFP deficiency is treated?

Early TFP deficiency
Most babies with early TFP deficiency die of heart or breathing problems, even when treated. However, treatment may help prolong life in some babies.

Childhood TFP deficiency
With prompt and careful treatment, children with TFP deficiency can often live healthy lives with typical growth and development. However, some children continue to have episodes of hypoglycemia or metabolic crisis, even with treatment. This can cause permanent brain damage and may result in learning disabilities or mental retardation.

Mild/muscle TFP deficiency
When treated, people with mild/muscle TFP deficiency usually remain healthy. This form does not affect intelligence.

If TFP deficiency is not treated, what problems occur?

TFP deficiency can cause mild symptoms in some people or more serious health problems in others. There are three forms of TFP deficiency: “early”, “childhood” and “mild”.

Babies and children with early and childhood TFP deficiency can have episodes of illness called metabolic crises. Some of the first symptoms of a metabolic crisis are:

  • extreme sleepiness
  • behavior changes
  • irritable mood
  • muscle weakness
  • poor appetite

Some of these other symptoms may also follow:

  • fever
  • nausea
  • diarrhea
  • vomiting
  • low blood sugar, called hypoglycemia
  • increased levels of acidic substances in the blood, called metabolic acidosis

If a metabolic crisis is not treated, a child with TFP deficiency can develop:

  • seizures
  • breathing problems
  • coma, sometimes leading to death

In children with TFP deficiency, either hypoglycemia or a metabolic crisis can happen:

  • after going too long without food
  • after long periods of exercise
  • during illness or infection
  • during times of stress, such as surgery  

Early TFP deficiency
Babies with early TFP deficiency usually show symptoms anywhere from birth through age two. The first symptoms are often:

  • poor appetite
  • sluggishness
  • extreme sleepiness
  • muscle weakness
  • absent reflexes
  • no response to pain
  • delays in walking and learning 

Babies with early TFP deficiency often have many episodes of metabolic crisis. 

Other effects of early TFP deficiency can include:

  • serious heart problems and enlarged heart
  • build-up of fat in the liver and other liver problems
  • breathing problems

Infants with early TFP who remain untreated usually die of heart or breathing problems by three years of age.

Childhood TFP deficiency
Childhood TFP deficiency can cause episodes of hypoglycemia and metabolic crisis. Between these episodes, children with TFP deficiency are usually healthy. However, repeated episodes may cause brain damage. This could result in learning problems or mental retardation.

Bouts of muscle weakness and pain happen in some children, especially after heavy exercise, stress or illness.

Mild/muscle TFP deficiency
The mild form of TFP deficiency has been reported in a small number of people. Symptoms can begin anywhere from age two to adulthood.

Episodes of muscle weakness are common. Breakdown of muscle fibers can occur. This usually happens:

  • after strenuous exercise or exertion 
  • during illness or infection
  • after going without food for a long period of time

Signs of muscle breakdown are:

  • muscle aches
  • cramps
  • weakness
  • reddish-brown color to the urine 
  • breathing problems

If muscle symptoms are not treated, kidney failure can occur.

The mild form of TFP deficiency does not cause metabolic crises or heart or liver problems. 

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FAMILY SUPPORT RESOURCES

Where can I find more information?

National Library of Medicine Genetics Home Reference: Mitochondrial Trifunctional Protein Deficiency http://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency

Fatty Oxidation Disorders (FOD) Family Support Group
http://www.fodsupport.org

Organic Acidemia Association
http://www.oaanews.org

United Mitochondrial Disease Foundation
http://www.umdf.org

CLIMB (Children Living with Inherited Metabolic Disorders)
http://www.climb.org.uk

Minnesota Family Support for Fatty Acid Oxidation Disorder (FAOD) - Contact: health.cyshn@state.mn.us

Minnesota Pediatric Metabolic Providers List

Medically Prescribed Formula: a table that provides a list of commonly prescribed medical foods and formulas and /or medication for this disorder.

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For additional genetics information and resources:

More help available from Children and Youth with Special Health Needs (CYSHN):

We would like to acknowledge the Star G Project. The information on the fact sheet was obtained from the Star G Project. For the most up-to-date information on the disorder please visit their web site at http://www.newbornscreening.info. Each fact sheet was extensively reviewed by family support groups, metabolic specialists across the country and the Star G steering committee.

THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content, including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET.
Updated Wednesday, 01-Aug-2012 13:57:49 CDT