Mitochondrial Trifunctional Protein Deficiency
What else is it called?
- TFP Deficiency
- Trifunctional Protein Deficiency
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What causes it?
This disorder belongs to a group known as the Fatty Acid Oxidation Disorders. Your body uses enzymes to break down fats. If there is a problem in one of these enzymes, your body will be unable to break down fats properly and cannot use the fat stored for energy.
TFP Deficiency is caused by a problem in the HADHA and HADHB genes. These genes are needed to make part of a complex of three enzymes. This is called the mitochondrial trifunctional protein which works together to break down certain types of fats. If not enough of this complex is produced, you will be unable to break down or convert these fats from food or stored fat to use as energy. This causes some of the symptoms of this disorder. Other symptoms are caused by the build-up of partially broken-down fats which can cause damage to the organs.
How common is it?
We do not know exactly how many people are affected by this disorder. The incidence is unknown. It is a rare disorder with fewer than 100 cases reported in literature.
What are the signs and symptoms?
Signs and symptoms may begin in infancy or later in life.
Long periods without food, illness/infection, periods of stress, or surgery can trigger serious episodes called metabolic crises. Symptoms of a metabolic crisis include:
- Irritability and/or changes in behaviour
- Muscle weakness
- Poor appetite
- Low blood sugar levels
- High levels of acids in the blood
- Diarrhoea & Vomiting
If a metabolic crisis is not treated, symptoms can quickly progress to breathing problems, seizures, and coma. If untreated, a metabolic crisis can be fatal.
Episodes of low blood sugar (hypoglycaemia) can occur without other symptoms of a crisis. Symptoms of hypoglycaemia include feeling weak, shaky, dizzy and clammy. Symptoms can progress and become severe if left untreated. Episodes of hypoglycaemia can be triggered by long periods without food, illness/infection, periods of stress, or surgery.
There are different types of TFP Deficiency which are classified by when the disorder first presents.
Early TFP Deficiency
This form begins in the neonatal period and is the most severe form. Symptoms include:
- Poor appetite
- Muscle weakness
- Absent reflexes
- No response to pain
- Delays in reaching developmental milestones
- An accumulation of fat in the liver (hepatic steatosis/fatty liver)
- Disease of the heart muscle (cardiomyopathy)
- Progressive muscle wasting and weakness (skeletal myopathy)
- Damage to the nerves (neuropathy)
The prognosis for this form of TFP Deficiency is very poor.
Childhood TFP Deficiency
This form usually presents between the neonatal period to 18 months of age. The disorder usually starts with an episode of hypoglycaemia or a metabolic crisis. As with other forms, these episodes and crises can be triggered by fasting, illness and stress. Generally, between the crises, this condition is manageable.
Repeated crises can cause damage to the brain causing developmental problems and intellectual disability. Heavy exercise, stress or illness can cause muscle weakness and pain.
Mild TFP Deficiency
The Mild form merges with the childhood form in symptoms, although there are no metabolic crises. It presents from a few months of age until adolescence. Episodes of muscle weakness and a break-down of much fibres can occur after heavy exercise, illness/infection, or long periods without food. When muscle fibres break down it can cause the urine to appear reddish-brown in colour and cause muscle aches and pain. In some cases, breathing problems may occur. This condition can progress to kidney failure if it is untreated
How is it diagnosed?
This disorder is diagnosed using specialised blood and urine tests. In some countries, it is screened for routinely at birth. Prenatal diagnosis is available if there is a known family history of TFP Deficiency.
Can it be treated?
There is no cure for TFP Deficiency. Treatment involves:
- A low-fat diet restricted in long chain fatty acids
- Medium chain fatty acid substitutes
- Avoidance of long periods without food and extreme cold
- Limited exercise, avoidance of over exertion
A specialist dietitian will help you to understand the diet. Any dietary changes must be approved and implemented by the dietitian.
When you receive your diagnosis you will be given an emergency regimen explaining what to do if you or your child becomes ill. This includes getting bugs such as vomiting, diarrhoea and fever. If you are unable to tolerate the regimen, continue to be ill and/or develop diarrhoea then you will need to be admitted to hospital to be given a glucose/dextrose drip as soon as possible. You will be given an emergency contact number to ring, however if this is unavailable call 999 for an ambulance or go to your nearest hospital’s accident and emergency (A&E) for treatment.
Do my family need to be tested?
Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes. We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.
This is an inherited condition. There is nothing that could have been done to prevent it.
Everyone has a pair of genes that make the mitochondrial trifunctional protein. In children with this condition, neither of these genes works correctly. These children inherit one non-working gene from each parent. Parents of children with this condition are carriers of the condition. Carriers do not have the disorder because the other gene of this pair is working correctly.
When both parents are carriers, in each pregnancy the risk to the baby is as follows:
- 25% chance (1 in 4) of the condition
- 50% chance (1 in 2) for the baby to be a carrier of the condition
- 25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier