General Condition Information
- TFP deficiency
- Trifunctional protein deficiency
The number of babies born with this very rare condition is currently unknown.
What is Mitochondrial trifunctional protein deficiency
The term mitochondrial trifunctional protein refers to a group of enzymes in your body that processes types of fat called long-chain fatty acids. These enzymes help break down these fatty acids so that your body can use them or get rid of them.
Without enough working mitochondrial trifunctional protein, the body has trouble using fats for energy. This condition can be more or less severe depending on how much mitochondrial trifunctional protein your baby can make.
Breaking down fat for energy allows your body to work properly, and it is especially important after a long time without food (fasting) and during illness. If your body does not make enough energy from fat, blood sugar levels can become dangerously low.
When fats are not processed, waste (including toxins) can build up. These toxins can damage your liver, heart, and muscles.
Newborn Screening and Follow-Up
Newborn screening for mitochondrial trifunctional protein deficiency is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures how much of certain substances (called acylcarnitines) are in your baby’s blood. Your body produces these substances when it makes energy from fats. Babies with high levels of these substances might have mitochondrial trifunctional protein deficiency.
If your baby’s blood spot screening result for mitochondrial trifunctional protein deficiency is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood and/or urine tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems soon after birth if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition are rare.
Some babies may have a false-positive result for mitochondrial trifunctional protein deficiency because their mother has high carnitine levels. These babies do not have and will not develop mitochondrial trifunctional protein deficiency. More testing on both mom and baby will determine who has high carnitine levels.
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs of mitochondrial trifunctional protein deficiency can vary widely and may appear anytime from a few months of age to childhood. They can be triggered by common illnesses (like a cold or flu) or a long time without food.
Signs of the condition may include the following:
- Problems feeding
- Weak muscle tone (hypotonia)
- Tiredness or lack of energy (lethargy)
- No reflexes or pain response
- Enlarged liver (hepatomegaly)
- Heart problems (cardiomyopathy)
- Low blood sugar (hypoglycemia)
The condition is caused by a change in the HADHA or HADHB gene. This gene gives the body instructions for making a complex enzyme called the mitochondrial trifunctional protein. This enzyme complex helps breaks down a certain type of fat, called long-chain fatty acids. This type of fat is an important source of energy for the heart, liver, and muscles.
Without a working HADHA or HADHB gene, your baby cannot make enough normal copies of mitochondrial trifunctional protein. As a result, the baby cannot properly break down fat to make energy and get rid of toxins.
- Mitochondrial trifunctional protein deficiency is an autosomal recessive condition. Babies inherit the condition when each parent passes down the same nonworking gene that causes mitochondrial trifunctional protein deficiency (HADHA or HADHB) to their baby. Only babies with two nonworking genes—for example, one nonworking HADHA from the mom and one nonworking HADHA from the dad—have this condition. Babies with two nonworking genes that do not match—for example, one nonworking HADHA from the mom and one nonworking HADHB from the dad—will not have this condition.
- People with one working copy and one nonworking copy of the HADHA or HADHB gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the HADHA or HADHB gene, they have a 1 in 4 chance of having a child with mitochondrial trifunctional protein deficiency.
- Carriers for mitochondrial trifunctional protein deficiency often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with mitochondrial trifunctional protein deficiency.
- Parents who already have a child with mitochondrial trifunctional protein deficiency still have a 1 in 4 chance of having another child with mitochondrial trifunctional protein deficiency. This 1 in 4 chance stays the same for all future children.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Regular and frequent meals and snacks
- Diet high in carbohydrates and low in fat
- Medium chain triglyceride (MCT) oil to help give the body fats it can break down
- L-carnitine supplements to help the body break down fats
- People with mitochondrial trifunctional protein deficiency must be very careful if they get sick and have vomiting or diarrhea, or do not want to eat. They may need emergency care to prevent low blood sugar levels.
Children who receive early and ongoing treatment for mitochondrial trifunctional protein deficiency can have healthy growth and development.