Proteins are the human body’s building blocks, and proteins are made of chains of molecules called amino acids, according to MedlinePlus. Nearly every cell in your body gets instructions from DNA on how to build proteins from amino acids. Depending on the way these proteins assemble, they can act as chemical messengers or form muscle, bone, ligaments, tendons, or tissue, according to Science News Explores. In some instances, the body produces an abnormal protein called amyloid, which can accumulate over time. And when enough of this amyloid builds up — either in one part of the body or in several places at once — the resulting symptoms and medical issues are known collectively as amyloidosis. (1) “To understand amyloid, you have to understand that everything your body produces is normally biodegradable and recyclable,” says Morie Gertz, MD, an amyloidosis expert and professor of medicine at the Mayo Clinic. “Amyloid is what happens when protein loses the ability to be degraded.” That happens because the protein molecules “misfold” and form a chemical structure that the body can’t break apart, Dr. Gertz says. Like that big island of floating plastic in the Pacific Ocean that keeps getting bigger and bigger, the amyloid your body can’t break apart continues to accumulate and eventually causes health issues. Collectively, the different types of amyloidosis affect fewer than 200,000 Americans, according to current estimates from the National Institutes of Health. (1) However, some experts who study the disease believe those government estimates may be way too low due to many patients being misdiagnosed or underdiagnosed. For instance, the National Organization for Rare Disorders estimates there are 4,000 new cases of AL amyloidosis, one of the most common amyloidosis types, per year. Nonetheless, experts agree that amyloidosis is a rare disease. There are roughly 30 varieties of abnormal protein that produce amyloid and that can therefore cause amyloidosis, says Raymond Comenzo, MD, a professor at the Tufts University School of Medicine in Boston and the director of the school’s John C. Davis Myeloma and Amyloid Program. But some types of protein are more likely than others to develop abnormalities. These are the most common types of amyloidosis and some of the proteins that cause them. AL amyloidosis starts in the blood cells produced in bone marrow, which is a fatty substance tucked inside the hollow chambers of bones. These blood cells are responsible for making antibodies that are part of your immune system’s defenses against foreign invaders, Gertz explains. In people with AL amyloidosis, some of these protein molecules — specifically, a kind called “light chain” proteins — don’t form properly. This improper assembly results in the buildup of amyloid. It’s not clear exactly why these protein molecules begin misassembling in the first place. (4) The problem with amyloidosis starting in bone marrow is that the resulting amyloid can accumulate in many different parts of the body — including the heart, kidneys, and gut. As a result, AL amyloidosis can cause a number of different symptoms. These include shortness of breath or an irregular heartbeat, swelling of the legs, tingling or loss of feeling in the arms or legs, and carpal tunnel syndrome. (5) AL amyloidosis is related to multiple myeloma, which is a type of cancer that starts in the same cells in the bone marrow. Some drugs developed to treat multiple myeloma can help people with AL amyloidosis, too. (4) RELATED: What Are the Treatment Options for Multiple Myeloma? Depending on how quickly someone with AL amyloidosis receives a correct diagnosis, drugs can be very effective, Gertz says. So can some types of bone marrow transplants, chemotherapy, and other symptom-specific treatments, he says. But just as AL amyloidosis symptoms vary a lot from one person with the condition to another, the prognosis also differs greatly from person to person. Learn More About AL Amyloidosis Causes, Symptoms, and Treatment These inflammatory diseases are in fact partly to blame for the development of AA amyloidosis. In response to inflammation, the liver produces high levels of a protein called serum amyloid A, or SAA. These SAA proteins help carry immune cells to inflamed parts of the body. But in patients who develop AA amyloidosis, the production of these SAA proteins is abnormal, and the body is unable to break apart the abnormal proteins from the healthy normal ones that carry immune cells throughout the body. (7) The problem tends to lead to the buildup of amyloid in a person’s kidneys. This buildup often causes a cluster of symptoms known as “nephrotic syndrome,” which includes high blood pressure, fatigue, unexplained weight gain, and other symptoms that also turn up in a range of unrelated health conditions. Other AA amyloidosis symptoms include: (7)
Frothy urine, which is caused by high levels of protein in a patient’s peeHigh cholesterolSwelling of the lower legsDiarrheaIrregular heartbeat
It’s not certain how many people develop AA amyloidosis each year, but the majority of cases turn up in developing countries where serious cases of inflammation-causing infections (such as tuberculosis) are more common. (8) AA amyloidosis can be deadly. But the average individual who develops the disease can live up to 13 years without treatment. There are a range of effective treatments for the disease, including inflammation-blocking drugs and those that slow or stop the accumulation of amyloid. Some dietary changes — including low-salt diets — can also help relieve some of the disease’s symptoms. Learn More About Why Some People Get AA Amyloidosis Both ATTR and non-TTR amyloidosis get the “TTR” part of their name from a blood protein called transthyretin. Transthyretin is a protein that helps carry some vitamins and hormones to different parts of the body.
ATTR Amyloidosis
ATTR amyloidosis usually affects adults between the ages of 20 and 70. While it’s thought to be rare, there’s some evidence that up to 4 percent of African-Americans carry the genetic variant that causes ATTR amyloidosis. (9) The symptoms of the disease depend on where in the body the amyloid builds up. Most cases of ATTR amyloidosis can be grouped into three categories: (10)
Non-TTR Amyloidosis
Non-TTR amyloidosis (as its name implies) is a genetic disorder that does not have to do with transthyretin. Instead, its associated genetic variants cause the abnormal production of other proteins, many of which play a role in kidney function. This can lead to kidney damage or disease, as well as heart problems, liver problems, nerve and/or muscle pain, and other symptoms and side effects common to a wide range of health conditions. (11) The specific treatments for the different types of ATTR and non-TTR amyloidosis depend a lot on an individual’s symptoms. Also, it’s important to note that the genetic variants that cause each of these diseases can be passed down from parent to child, but they can also form spontaneously, meaning they just show up. A person who has the gene mutation, whether inherited or spontaneous, can pass it on to his or her children. (9) Learn More About the Types of Hereditary Amyloidosis In fact, it’s still not completely clear why the TTR proteins become abnormal in people with this type of amyloidosis. Age and sex seem to be big factors: more than 70 percent of individuals with wild-type ATTR are men, and the mean age of symptom onset was mid-50s. (13) By some estimates, up to 1 percent of all adults age 80 and older have some amyloid buildup associated with wild-type ATTR. (14) In up to 50 percent of individuals with wild-type ATTR, the amyloid buildup happens in the person’s heart. This amyloid buildup can lead to symptoms like dizziness, fatigue, leg swelling, shortness of breath, and an unusual heartbeat. It can also contribute to hypertension. (12) While no one is certain why, Dr. Comenzo says one theory is that wild-type ATTR is much more common than formal estimates suggest because it may in many cases never be diagnosed. In many cases, it may be an underlying cause of heart failure because standard tests to monitor cardiovascular conditions may not be able to identify amyloidosis. (12,15) Nerve-related trouble is also common in people with wild-type ATTR amyloidosis. In these cases, the disease can cause pain, tingling, or loss of feeling in a person’s arms or legs. Carpal tunnel syndrome — a numbness or tingling in the hand and arm — is also common. In fact, carpal tunnel syndrome is often the earliest symptom of the disease. (12) However, this form of amyloidosis tends to progress very slowly. It may contribute to heart trouble or other potentially life-threatening health conditions, but it’s not clear how often wild-type ATTR is the sole cause or driving force behind these issues. In fact, many people with this type of amyloidosis may never experience symptoms. (6,13) It’s important to note that further research is needed to understand what causes wild-type ATTR amyloidosis. Experts are only now getting a good grip on the disease’s commonness and symptoms, and so the thinking on it may soon shift, Comenzo says. Learn More About Wild-Type ATTR Amyloidosis While ALECT2 seems to be quite rare, there’s evidence that it shows up much more commonly in people of Hispanic ancestry. (17) Not a lot is known about the disease, but the current research suggests it’s not typically fatal, especially with medical intervention. A 2018 study found that 60 percent of patients with ALECT2 amyloidosis (without involvement of the heart) are projected to survive more than 10 years. Another study found only 6 percent of people diagnosed with the disease died as a result, and roughly 30 percent have stable kidney function following treatment. (18) Learn More About What Doctors Know About ALECT2 Amyloidosis Beta-2 Microglobulin (B2M) Amyloidosis This type of amyloidosis involves the erred folding of a protein found on the surface of white blood cells. B2M amyloidosis typically occurs as a complication in people who are experiencing kidney failure following many years of dialysis treatment. Amyloid tends to build up around a patient’s bones and joint-related tissues. Carpal tunnel syndrome and nerve pain or stiffness are the most common symptoms. This type is also sometimes called DRA (which stands for dialysis-related amyloidosis). (19) Apolipoprotein Amyloidosis This type involves proteins that play a role in transporting or breaking down cholesterol and fat. There are at least five subtypes of apolipoprotein amyloidosis, several of which are hereditary, and each can affect different parts of the body and cause varying symptoms, from kidney problems to heart problems to nervous system problems. (20) Hereditary Fibrinogen Amyloidosis Sometimes called AFib amyloidosis, this type affects a protein that plays a role in blood clotting. It’s hereditary and can be caused by any of 16 different genetic mutations that result in amyloid accumulating in a patient’s kidneys. (20) Hereditary Gelsolin Amyloidosis Known also as AGel amyloidosis, this type results from amyloid produced by a protein that normally helps give cells shape and structure. It is a hereditary type of amyloidosis, and it tends to affect a patient’s cranial nerves, eyes, skin, or kidneys. (20) Hereditary Lysozyme Amyloidosis Sometimes called ALys amyloidosis, the type of amyloid formed involves the accumulation of abnormal lysozyme protein, which is an enzyme found in tears and mucus that normally helps the body break down invading bacteria, according to a 2022 paper. ALys is another hereditary amyloidosis, and it can affect the function of multiple organs or systems, including the GI system. (20) Even for patients who are diagnosed with amyloidosis, the road to that diagnosis is usually long and difficult. Many patients see multiple doctors, and it may take a year or two to receive an accurate diagnosis, Comenzo says. How is that diagnosis made? Urine and blood tests are two preliminary types of analysis that can point to the presence of amyloid buildup. “Protein in urine is a very powerful indicator of amyloidosis,” Gertz says. “It’s not routine to do this kind of urine analysis, but it’s a simple test.” In addition to (and often, following) those urine and blood tests, doctors will perform tissue biopsies to look for amyloid deposits. They’ll also analyze the amyloid to determine which particular type of protein or protein abnormality is causing the patient’s amyloidosis, Comenzo says. If you believe you may have amyloidosis, you shouldn’t feel shy about bringing it up with your doctor, he says. It may take some time — and a lengthy process of elimination — for your doctor to determine if amyloidosis is the cause of your health issues. Learn More About How Doctors Diagnose Amyloidosis
