Familiar amyloid polyneuropathy (FAP) is a rare genetic condition that is difficult to diagnose because it shares symptoms with other neuropathic disorders, most of which are more common.
In areas where the disease is endemic, or in people with a family history of disease, diagnoses typically occur within a year. In regions where FAP is less common, delays of three to four years in diagnosis happen often.
Initially, the doctor will observe the patient for a period of time to understand their symptoms and examine their family history. The physician will then analyze the findings from physical and neurologic examinations and order additional tests to rule out other conditions that may cause similar symptoms.
Conclusive diagnostic tests
A conclusive diagnosis of FAP can only be made through genetic testing and tissue biopsy.
Genetic testing analyzes the sequence of the TTR gene to identify mutations that cause the disease. These mutations lead to a buildup of abnormal protein deposits, called amyloid fibrils, which damage the body’s tissues and organs.
The testing is usually performed on DNA extracted from blood samples drawn from a patient’s vein. There are more than 130 mutations in the TTR gene known to cause FAP, and different mutations have been associated with different symptoms and disease courses.
Since FAP is caused by mutations, genetic testing is essential for a conclusive diagnosis. However, to distinguish symptomatic patients from carriers — those who harbor a genetic mutation but have no symptoms of the disease — a tissue biopsy is needed to evaluate the presence of amyloid fibrils within body tissues.
Tissue biopsy is the “gold standard” test to detect amyloid fibrils. A small piece of an affected tissue or organ, such as a nerve or fat in the stomach area, is taken using a needle.
The sample is processed in the laboratory, usually with a dye called Congo red to stain and identify amyloid fibrils, and then examined under a microscope. If amyloid fibrils are present, then the sample has a characteristic “apple green” appearance, which changes to red as the plane of polarized light is rotated.
The presence of amyloid fibrils can be confirmed using specific antibody molecules (proteins) that are designed to bind, recognize, and distinguish different types of amyloid fibrils. Mass spectrometry can also be useful for differentiating types of amyloid fibrils.
Other diagnostic tests
An electromyogram assesses the health of muscles and the nerves that control them. This test allows physicians to measure the electrical activity of patient muscle cells, by inserting a needle-like electrode into a specific muscle during a contraction. Electrical signals generated by muscle cells are recorded and then analyzed to assess muscle health.
Nerve conduction velocity test
The nerve conduction velocity (NCV) test measures the strength and speed at which a nerve is able to transmit an electrical signal to other areas of the body. The test is performed by placing electrodes on the surface of the skin at various points over a nerve. One electrode delivers small electrical shocks to the nerve, while the other records the nerve’s responses. In FAP patients, NCV is often decreased.
Tilt table test
This test monitors the response of blood pressure and heart rate to changes in posture and position. The patient lies flat on a table, with the upper part of the body tilted in the upright position. Normally, blood vessels become narrower and heart rate increases to compensate for the drop in blood pressure. This response may be slowed or abnormal if the patient has autonomic neuropathy, a condition sometimes seen in those with FAP.
Thermoregulatory sweat test
This test measures the function of nerves controlling the body’s response to changes in temperature. It is usually done in a laboratory setting where temperatures can be carefully controlled. People with FAP may be less able to sense and respond to temperature changes.
These tests are used to check for abnormalities in digestion, such as slow digestion and delayed stomach emptying. Broadly, they involve having a person ingest a substance that can be detected at various points in the digestive tract. For example, some tests require patients to eat a light meal that contains a small amount of radioactive material. A scanner can then detect when the material leaves the stomach and determine whether digestion is taking place at a normal pace.
Quantitative sensory testing
Quantitative sensory testing comprises a battery of tests that are meant to evaluate a person’s ability to sense various stimuli normally, ranging from feeling vibrations and pressure, to sensing pain and heat.
Heart health assessments
Tests to evaluate heart health may include echocardiography to detect an enlargement of the heart caused by the buildup of amyloid deposits, as well as an electrocardiogram and Holter monitor to help detect abnormalities in the heart’s electrical activity. Magnetic resonance imaging can also be used to image the heart and detect abnormalities.
A blood test to measure the levels of NT-proBNP (N-terminal of the prohormone brain natriuretic peptide) or troponin may also be used to assess heart health since elevated levels can indicate heart injury.
In some cases, FAP can cause damage to the eyes. Thus, regular eye exams are recommended to monitor the course of FAP and help identify its presence.
Kidney health assessments
In some FAP patients, kidney health is also impaired. Impairments in kidney function can be assessed by measuring the levels of proteins and other substances in the urine, as well as through specific blood tests. Clinicians may use these tests to calculate the estimated glomerular filtration rate, which basically indicates how well kidneys are able to filter waste products from the bloodstream.
Last updated: June 8, 2021
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