Mitochondrial trifunctional protein deficiency

autorecessive

Mitochondrial trifunctional protein deficiency (MTPD) is a rare, autosomal recessive metabolic disorder that impacts the body's ability to convert certain fats into energy. This condition is part of a group of disorders known as fatty acid oxidation disorders. The mitochondrial trifunctional protein is a complex enzyme located in the mitochondria, responsible for the last three steps of long-chain fatty acid oxidation. Deficiency in this protein affects the body's lipid metabolism, leading to a wide range of clinical manifestations, from mild to severe.

Symptoms

The symptoms of mitochondrial trifunctional protein deficiency can vary widely among affected individuals. They can range from mild muscle pain and fatigue to more severe complications such as hypoglycemia (low blood sugar), cardiomyopathy (heart muscle disease), liver dysfunction, and neuropathy (nerve damage). In infants, the disease often presents as life-threatening heart and liver problems. The severity and onset of symptoms are influenced by the specific mutations in the genes encoding the trifunctional protein complex.

Causes

Mitochondrial trifunctional protein deficiency is caused by mutations in the HADHA and HADHB genes. These genes provide instructions for making the subunits of the mitochondrial trifunctional protein complex. Mutations in these genes reduce or eliminate the activity of the enzyme complex, leading to the accumulation of unprocessed fatty acids in the body's tissues, which can cause the symptoms and complications associated with the disorder.

Diagnosis

Diagnosis of mitochondrial trifunctional protein deficiency typically involves a combination of clinical evaluation, biochemical tests, and genetic testing. Biochemical tests can detect abnormalities in the blood and urine that are indicative of impaired fatty acid oxidation. Genetic testing can identify mutations in the HADHA and HADHB genes, confirming the diagnosis.

Treatment

There is no cure for mitochondrial trifunctional protein deficiency, but treatment focuses on managing symptoms and preventing metabolic crises. Dietary management, including a low-fat, high-carbohydrate diet with medium-chain triglyceride (MCT) supplementation, is often recommended to avoid fasting and manage energy needs. In some cases, individuals may require carnitine supplementation to help transport fatty acids into mitochondria for energy production. Regular follow-up with a team of specialists, including a metabolic geneticist, cardiologist, and nutritionist, is essential for managing the condition.

Prognosis

The prognosis for individuals with mitochondrial trifunctional protein deficiency varies depending on the severity of the disease and the age at diagnosis. Early diagnosis and management can improve the quality of life and reduce the risk of severe complications. However, individuals with severe forms of the disease may have a significantly shortened lifespan, particularly if diagnosed in infancy.