Trifunctional Protein (TFP) Deficiency
TFP deficiency is inherited in an autosomal recessive pattern. Normally a person has two functional genes (HADHA and HADHB). In people with TFP deficiency, both copies of either the HADHA gene or HADHB gene have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with TFP deficiency typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of TFP deficiency do not typically have symptoms. However, a mother who is pregnant with a baby with TFP deficiency is at risk of illness during pregnancy. The mother may develop HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) or AFLP (acute fatty liver of pregnancy).
Infants with the most severe form of the disease begin having symptoms as newborns, including hypoglycemia (low blood sugar), liver problems and cardiomyopathy (disease of the heart muscle). Most infants with this severe form die within the first few months of life.
The symptoms of less severe TFP deficiency may begin anytime during infancy through early childhood. They vary from one individual to the next, but may include hypoglycemia (low blood sugar), liver problems, cardiomyopathy (disease of the heart muscle), retinopathy (disease of the eye) and hypotonia (low muscle tone). Later in childhood, rhabdomyolysis (muscle breakdown) and muscle pain may occur.
The mildest form of TFP deficiency can begin anytime from childhood to adulthood. Symptoms include rhabdomyolysis (muscle breakdown) during exercise and peripheral neuropathy (nerve disorder in the limbs).
- Incidence: The overall incidence is unknown.
- New York State Method of Screening (First Tier): Screening for TFP deficiency is accomplished by measuring acylcarnitines (C16OH and C18:1OH) by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Screening may be normal in patients with mild TFP deficiency who were recently fed, received IV glucose or were not ill when the specimen was collected. Newborn screening cannot distinguish between TFP deficiency and Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.
- Interpretation/reporting of data: Results are reported as screen negative or as a referral. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for TFP deficiency are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of TFP deficiency.
Diagnostic testing may include quantification of plasma acylcarnitines, molecular genetic testing of the gene and functional analysis of fatty acid oxidation on fibroblasts (skin cells).
Treatment is dietary, including avoidance of fasting, drinking low-fat formula and supplementation with medium-chain triglycerides (MCT) as a source of supplemental calories. Treatment for cardiac involvement or rhabdomyolysis is supportive. During times of illness, hospitalization may be required to monitor and treat hypoglycemia.
Prognosis of the severe form is poor and most infants die in the first few months of life. Prognosis of the milder forms is variable, and dependent on multiple factors, including the severity of disease and response to treatments.
Trifunctional protein (TFP) deficiency is a fatty acid oxidation disorder (inherited metabolic disorder).
TFP deficiency is caused by mutations in the HADHA and HADHB genes. Individuals with this disorder are unable to convert certain fats to energy and may develop symptoms during times of high energy need such as fasting or illness.