AMYLOIDOSIS AWARENESS:
XAVIER'S LEGACY
Amyloidosis
What is Amyloidosis?
Amyloidosis is a rare disease that occurs when abnormal proteins called amyloid build up in various tissues and organs in the body, interfering with their normal function. The amyloid protein is produced in the bone marrow and can accumulate in any part of the body, including the heart, kidneys, liver, spleen, nervous system, and digestive tract.
What are the symptoms?
The symptoms of amyloidosis vary depending on which organs are affected and can include fatigue, weakness, weight loss, swelling, numbness or tingling in the hands and feet, shortness of breath, irregular heartbeat, and gastrointestinal problems.
How can it be diagnosed?
The diagnosis of amyloidosis typically involves a biopsy of the affected tissue or organ and blood tests to detect abnormal proteins.
Can it be treated?
Treatment options include chemotherapy, stem cell transplantation, and medication to manage symptoms.
Are there different types of Amyloidosis?
Yes, there are different types of amyloidosis, including primary (AL), secondary (AA), hereditary (ATTR), and dialysis-related (Aβ2M).
AA amyloidosis is caused by chronic inflammatory conditions, such as rheumatoid arthritis or inflammatory bowel disease, which trigger the production of amyloid proteins.
ATTR amyloidosis is a hereditary form caused by genetic mutations that affect the production of certain proteins in the body.
Aβ2M amyloidosis is a complication of long-term hemodialysis treatment for kidney failure, caused by the accumulation of beta-2 microglobulin protein in the blood.
Primary (AL) Amyloidosis:
One of the unique features of primary amyloidosis (AL amyloidosis) is that it is caused by the production of abnormal light chains by plasma cells in the bone marrow, which then clump together and form amyloid deposits in various organs and tissues throughout the body.
Unlike other types of myloidosis, such as secondary amyloidosis which occurs as a result of chronic inflammation, or hereditary amyloidosis which is caused by genetic mutations, primary amyloidosis is not directly linked to any other underlying condition or inherited trait. Another unique aspect of AL amyloidosis is that it can affect multiple organs at the same time, leading to a wide range of symptoms and complications. Additionally, because the symptoms of AL amyloidosis can be similar to those of other conditions, it can be challenging to diagnose, requiring specialized tests to detect the presence of amyloid deposits. While primary amyloidosis is a serious condition that can have a significant impact on a person's quality of life, recent advances in treatment options have led to improved outcomes and longer survival rates for many patients.
Secondary (AA) amyloidosis:
Also known as reactive amyloidosis, this occurs as a complication of another underlying condition, usually a chronic inflammatory or infectious disease such as rheumatoid arthritis, tuberculosis, or inflammatory bowel disease. In secondary amyloidosis, chronic inflammation leads to the production of a protein called serum amyloid A (SAA), which then clumps together and forms amyloid deposits in various organs and tissues throughout the body, interfering with their normal functioning. Treatment for secondary amyloidosis is focused on controlling the underlying condition that is causing the chronic inflammation, which will reduce the production of SAA and in turn slow down the progression of the disease. Medications such as corticosteroids or immunosuppressants may be used to manage inflammation. In severe cases, organ-specific treatments may be required, such as dialysis for kidney failure or a liver transplant for liver failure.
ATTR amyloidosis:
ATTR amyloidosis (transthyretin amyloidosis) is a type of hereditary amyloidosis caused by the accumulation of misfolded transthyretin (TTR) protein in various tissues throughout the body. TTR is normally produced in the liver and is involved in transporting thyroid hormone and vitamin A throughout the body. In ATTR amyloidosis, a genetic mutation causes the TTR protein to misfold and form amyloid deposits in tissues such as the heart, nerves, and gastrointestinal system. The accumulation of amyloid deposits can impair the function of these organs, leading to symptoms such as heart failure, peripheral neuropathy, and gastrointestinal disturbances. ATTR amyloidosis can be inherited in an autosomal dominant manner, meaning that a person only needs to inherit one copy of the mutated gene from one parent to develop the condition. The clinical presentation of ATTR amyloidosis can vary widely depending on the organs affected and the severity of amyloid deposition. Treatment options may include supportive care, organ-specific management of complications, and potentially, liver or heart transplantation.
Dialysis-related (DRA/Aβ2M) amyloidosis:
Dialysis-related amyloidosis (DRA) can occur in individuals with end-stage kidney disease who have been on long-term dialysis treatment. DRA is caused by the accumulation of a protein called beta-2 microglobulin (β2M), which is a normal protein found in the blood that is usually filtered out by the kidneys. In individuals with end-stage kidney disease, the kidneys are no longer able to filter β2M out of the blood, causing it to build up in the body. Over time, the excess β2M can clump together and form amyloid deposits in various tissues throughout the body, including the bones, joints, and tendons. This can lead to joint pain, stiffness, and limited mobility. DRA can also affect the carpal tunnel, causing numbness, tingling, and weakness in the hands. In rare cases, DRA can affect other organs such as the heart, lungs, and liver, which can cause serious complications. Diagnosis of DRA is typically done through a biopsy of the affected tissue or organ, which will show the presence of β2M amyloid deposits. Blood tests can also be done to measure the levels of β2M in the blood. Treatment for DRA typically involves controlling the underlying condition, end-stage kidney disease, through dialysis or kidney transplantation. However, DRA is a chronic condition that may persist even after kidney transplantation, and additional treatments may be necessary to manage symptoms and complications. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids may be used to manage joint pain and inflammation, and surgical intervention may be necessary in severe cases.
AFib (fibrinogen A alpha-chain) amyloidosis:
AFib (fibrinogen A alpha-chain) amyloidosis is a type of hereditary amyloidosis caused by the buildup of abnormal fibrinogen A alpha-chain protein in various tissues throughout the body. This protein is normally produced in the liver and is involved in blood clotting. In people with AFib amyloidosis, a genetic mutation causes the fibrinogen A alpha-chain protein to be misfolded, leading to the formation of amyloid deposits in organs such as the kidneys, liver, and spleen. These amyloid deposits can impair organ function, leading to symptoms such as kidney dysfunction, liver enlargement, and gastrointestinal disturbances.
AFib amyloidosis is a rare form of amyloidosis, and its clinical presentation can vary widely depending on the organs affected and the severity of amyloid deposition. Treatment options may include supportive care, management of organ-specific complications, and potentially, organ transplantation.
ApoA1 (apolipoprotein A-1) amyloidosis
ApoA1 (apolipoprotein A-1) amyloidosis is a type of hereditary amyloidosis caused by the accumulation of misfolded ApoA1 protein in various tissues throughout the body. ApoA1 is a protein that is a major component of high-density lipoprotein (HDL), also known as "good" cholesterol, and plays a role in cholesterol metabolism and transport. In ApoA1 amyloidosis, a genetic mutation causes the ApoA1 protein to misfold and form amyloid deposits in organs such as the kidneys, liver, and spleen. The accumulation of amyloid deposits can impair organ function, leading to symptoms such as kidney dysfunction, liver enlargement, and gastrointestinal disturbances. ApoA1 amyloidosis is a rare form of amyloidosis, and its clinical presentation can vary widely depending on the organs affected and the severity of amyloid deposition. Treatment options may include supportive care, management of organ-specific complications, and potentially, organ transplantation.
APrP (prion protein) amyloidosis
APrP (prion protein) amyloidosis, also known as prion disease, is a rare and fatal neurodegenerative disorder caused by the accumulation of abnormal prion protein in the brain. Prion protein is a naturally occurring protein found in healthy cells throughout the body, but in prion disease, the protein becomes misfolded, leading to the formation of amyloid deposits in the brain. The accumulation of amyloid deposits in the brain leads to the destruction of brain tissue and the progressive deterioration of neurological function. The disease can manifest in different forms, including Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Prion disease is a very rare disorder, affecting fewer than one in a million people worldwide. There is currently no cure for prion disease, and treatment is primarily focused on relieving symptoms and improving quality of life.
Gelsolin amyloidosis
Gelsolin amyloidosis is a rare hereditary disorder caused by a genetic mutation that leads to the accumulation of misfolded gelsolin protein in various tissues throughout the body. Gelsolin is a protein that plays a role in regulating the structure and function of cells. In gelsolin amyloidosis, the mutated gelsolin protein forms amyloid deposits that can accumulate in organs such as the nerves, skin, and eyes, leading to symptoms such as peripheral neuropathy, skin lesions, and vision problems. Gelsolin amyloidosis is a rare form of amyloidosis, and its clinical presentation can vary widely depending on the organs affected and the severity of amyloid deposition. Treatment options may include supportive care, management of organ-specific complications, and potentially, organ transplantation.
Cystatin C amyloidosis
Cystatin C amyloidosis is a rare type of hereditary amyloidosis caused by a genetic mutation that leads to the accumulation of misfolded cystatin C protein in various tissues throughout the body. Cystatin C is a protein that plays a role in regulating the activity of enzymes that break down proteins. In cystatin C amyloidosis, the misfolded cystatin C protein forms amyloid deposits that can accumulate in organs such as the kidneys, liver, and spleen, leading to symptoms such as kidney dysfunction, liver enlargement, and gastrointestinal disturbances. Cystatin C amyloidosis is a rare form of amyloidosis, and its clinical presentation can vary widely depending on the organs affected and the severity of amyloid deposition. Treatment options may include supportive care, management of organ-specific complications, and potentially, organ transplantation.
Lysozyme amyloidosis
Lysozyme amyloidosis is a rare type of hereditary amyloidosis caused by a genetic mutation that leads to the accumulation of misfolded lysozyme protein in various tissues throughout the body. Lysozyme is a protein that plays a role in breaking down bacterial cell walls. In lysozyme amyloidosis, the misfolded lysozyme protein forms amyloid deposits that can accumulate in organs such as the liver, spleen, and kidneys, leading to symptoms such as liver enlargement, kidney dysfunction, and gastrointestinal disturbances. Lysozyme amyloidosis is a rare form of amyloidosis, and its clinical presentation can vary widely depending on the organs affected and the severity of amyloid deposition. Treatment options may include supportive care, management of organ-specific complications, and potentially, organ transplantation.
Senile systemic amyloidosis
Senile systemic amyloidosis (SSA) is a type of amyloidosis that occurs in elderly individuals, typically over the age of 70. It is characterized by the deposition of amyloid fibrils made up of a protein called transthyretin (TTR) in various organs throughout the body, including the heart, kidneys, and nervous system. In SSA, the amyloid fibrils accumulate slowly over time and can interfere with the normal function of affected organs. Common symptoms include heart failure, kidney dysfunction, and peripheral neuropathy. Unlike other types of TTR amyloidosis, SSA is not caused by a genetic mutation, but rather by age-related changes in the structure of the TTR protein that make it more likely to form amyloid fibrils. Treatment options for SSA depend on the severity and extent of organ involvement, and may include supportive care, medication to manage symptoms, and potentially, organ transplantation.
Alzheimer's disease
Alzheimer's disease is considered to be an amyloidosis disease because it is characterized by the accumulation of abnormal protein aggregates called amyloid plaques in the brain. Specifically, the plaques are composed of a protein called beta-amyloid, which is produced from a larger protein called amyloid precursor protein (APP). However, Alzheimer's disease is a complex and multifactorial disease, and the role of beta-amyloid accumulation in the development and progression of the disease is still a subject of research and debate among scientists. Other factors, such as inflammation and the accumulation of another protein called tau, also play a role in the development and progression of Alzheimer's disease.
Type 2 diabetes mellitus
Type 2 diabetes mellitus is not typically considered to be an amyloidosis disease because it is not caused by the accumulation of amyloid fibrils in tissues. However, there is growing evidence to suggest that the misfolding and aggregation of specific proteins, such as islet amyloid polypeptide (IAPP or amylin), may contribute to the development and progression of type 2 diabetes. In type 2 diabetes, there is a dysfunction of pancreatic beta cells, which normally produce and secrete insulin. The accumulation of misfolded and aggregated IAPP in the pancreatic islets of Langerhans has been implicated in this dysfunction, leading to beta cell death and insulin resistance. While the accumulation of misfolded proteins in type 2 diabetes is not considered to be a classic form of amyloidosis, it does involve the misfolding and aggregation of specific proteins, and there is ongoing research into the role of protein misfolding and aggregation in the pathogenesis of the disease.
Atherosclerosis-associated amyloidosis
Atherosclerosis-associated amyloidosis is a type of localized amyloidosis that occurs in the walls of blood vessels affected by atherosclerosis, a condition characterized by the buildup of fatty deposits (plaque) in the arteries. In this type of amyloidosis, the amyloid deposits are derived from a protein called serum amyloid A (SAA), which is produced in response to inflammation in the body. SAA is transported in the blood by high-density lipoprotein (HDL) particles, commonly known as "good cholesterol." However, in the presence of chronic inflammation, such as that seen in atherosclerosis, SAA can become abnormally folded and form amyloid fibrils that deposit in the arterial walls. The amyloid deposits in atherosclerosis-associated amyloidosis are typically localized to the intima (innermost layer) of the arterial wall, where they can cause stiffening and thickening of the vessel wall. This can contribute to the progression of atherosclerosis and increase the risk of complications such as heart attack and stroke. Atherosclerosis-associated amyloidosis is considered to be a rare form of localized amyloidosis and is typically diagnosed incidentally during imaging or biopsy of affected blood vessels. Treatment typically involves managing the underlying atherosclerosis and associated risk factors, such as hypertension and hyperlipidemia, to slow or prevent further progression of the disease.
Isolated atrial amyloidosis (IAA)
Isolated atrial amyloidosis (IAA) is a localized form of amyloidosis that affects the atria (upper chambers) of the heart. It is a type of amyloidosis that is specific to the heart and does not involve other organs or tissues. IAA is characterized by the deposition of amyloid fibrils made up of a protein called transthyretin (TTR) in the atrial tissue. The accumulation of these fibrils can cause structural changes in the atria, including thickening and stiffness of the atrial walls. Over time, this can impair the ability of the atria to contract and pump blood effectively, leading to various symptoms such as palpitations, shortness of breath, and fatigue. IAA is often associated with other forms of amyloidosis, particularly hereditary TTR amyloidosis (ATTR), which is caused by mutations in the TTR gene. However, IAA can also occur in individuals without a known genetic mutation. IAA is typically diagnosed through a combination of imaging tests (such as echocardiography or cardiac MRI) and biopsy of the atrial tissue to confirm the presence of amyloid deposits. Treatment may involve medications to manage symptoms and reduce the risk of complications, as well as interventions such as ablation or pacemaker implantation to restore normal heart rhythm. In some cases, heart transplantation may be necessary to treat severe cases of IAA.
Osteomyelitis-associated amyloidosis
Osteomyelitis-associated amyloidosis is a rare type of localized amyloidosis that occurs in individuals with chronic osteomyelitis, which is a bacterial infection of the bone. In this type of amyloidosis, the chronic infection causes inflammation and tissue damage, leading to the formation of amyloid deposits in the affected bone and surrounding tissue. The amyloid fibrils in this type of amyloidosis are typically composed of the protein serum amyloid A (SAA). Osteomyelitis-associated amyloidosis may cause a range of symptoms depending on the location and severity of the infection and amyloid deposition. These may include chronic pain, swelling, fever, and bone deformity. In some cases, the amyloid deposits may also damage nearby nerves or blood vessels, leading to further complications. Diagnosis of osteomyelitis-associated amyloidosis typically involves a combination of imaging tests, such as X-rays or MRI, and biopsy of the affected tissue to confirm the presence of amyloid deposits. Treatment may involve antibiotics to manage the underlying infection, as well as medications to manage symptoms and reduce inflammation. In severe cases, surgical intervention may be necessary to remove infected or damaged tissue.
Cerebral amyloid angiopathy (CAA)
Cerebral amyloid angiopathy (CAA) is a type of amyloidosis that affects the blood vessels in the brain. In CAA, abnormal protein deposits, called amyloid fibrils, accumulate in the walls of small and medium-sized blood vessels in the brain, leading to damage and impaired blood flow. The amyloid fibrils in CAA are typically composed of the protein beta-amyloid, which is also the main component of the amyloid plaques found in the brains of individuals with Alzheimer's disease. However, in CAA, the amyloid deposits are specifically localized to the blood vessels. CAA can cause a range of neurological symptoms depending on the location and severity of the amyloid deposition. These may include cognitive decline, headaches, seizures, stroke-like symptoms, and neurological deficits such as weakness or numbness. Diagnosis of CAA typically involves a combination of brain imaging tests, such as MRI or CT scans, and examination of brain tissue samples obtained through biopsy or autopsy. There is no specific treatment for CAA, but management may involve medications to control symptoms and prevent complications, such as anticoagulants to reduce the risk of stroke. In some cases, surgery may be necessary to remove blood clots or repair damaged blood vessels.
Gelatinous drop-like corneal dystrophy (GDLD)
Gelatinous drop-like corneal dystrophy (GDLD) is a rare inherited disorder that affects the cornea, the clear front surface of the eye. In GDLD, abnormal protein deposits, called amyloid fibrils, accumulate in the cornea, leading to clouding and loss of vision. GDLD is typically diagnosed in childhood or early adulthood and can cause a range of symptoms, including decreased visual acuity, sensitivity to light, and a sensation of foreign body in the eye. The amyloid deposits in GDLD are composed of a protein called transforming growth factor beta-induced (TGFBI) protein.
There is no cure for GDLD, and treatment is focused on managing symptoms and preventing complications. In some cases, corneal transplantation may be necessary to restore vision. However, recurrence of the amyloid deposits in the transplanted cornea is a common problem, and long-term outcomes are generally poor. Research is ongoing to better understand the underlying mechanisms of GDLD and to develop new treatments for the disorder.
Lattice corneal dystrophy (LCD)
Lattice corneal dystrophy (LCD) is a type of inherited corneal disease that is characterized by the accumulation of abnormal protein deposits, called amyloid fibrils, in the cornea. These amyloid fibrils are composed of a specific protein called TGFBI (transforming growth factor beta-induced) protein, which is produced by cells in the cornea. The accumulation of TGFBI protein leads to the formation of lattice-like patterns in the cornea, which can cause vision problems such as blurred or distorted vision. Over time, the amyloid deposits can cause scarring in the cornea, which can lead to more severe vision impairment. LCD is classified as a type of localized amyloidosis, where the amyloid deposits are restricted to a specific tissue or organ, in this case, the cornea.
Keratoconus-associated corneal amyloidosis
Keratoconus-associated corneal amyloidosis is a type of localized amyloidosis that affects the cornea of the eye. Keratoconus is a condition in which the cornea becomes thin and weak, leading to a cone-shaped bulge that can cause visual distortion. In some cases of keratoconus, amyloid deposits can also accumulate in the cornea, leading to further visual problems. The amyloid deposits are composed of a protein called keratoepithelin, which is produced by the cells in the cornea. The accumulation of keratoepithelin protein can lead to a gradual clouding of the cornea, which can worsen vision over time. Treatment for keratoconus-associated corneal amyloidosis may involve the use of contact lenses, corneal cross-linking, or in more severe cases, corneal transplant surgery.
LECT2 amyloidosis
LECT2 amyloidosis is a rare type of amyloidosis that is caused by the buildup of amyloid deposits made up of a protein called leukocyte chemotactic factor 2 (LECT2). It can affect various organs, including the liver, kidneys, spleen, and adrenal glands. Symptoms may include liver dysfunction, kidney failure, and other organ dysfunction depending on the organs affected. It is believed to be inherited in an autosomal dominant pattern.
ALECT2 (leukocyte cell-derived chemotaxin 2)-associated amyloidosis
ALECT2 (leukocyte cell-derived chemotaxin 2)-associated amyloidosis is a type of systemic amyloidosis that is caused by the deposition of amyloid protein composed of leukocyte cell-derived chemotaxin 2 (LECT2) in various organs of the body. LECT2 is a protein produced by the liver and is involved in regulating immune response and inflammation.
ALECT2 amyloidosis typically affects the kidneys and liver, but can also affect other organs such as the spleen and adrenal glands. Symptoms of ALECT2 amyloidosis can vary depending on the affected organs but may include proteinuria (protein in urine), nephrotic syndrome (a kidney disorder characterized by high levels of protein in urine), and hepatomegaly (enlarged liver).
ALECT2 amyloidosis is a rare disease, and little is known about its causes or treatment. Diagnosis of ALECT2 amyloidosis is typically made by a biopsy of the affected organ and confirmed through laboratory analysis of the amyloid protein.
ALECT2 (leukocyte cell-derived chemotaxin 2)-associated amyloidosis
ALECT2 (leukocyte cell-derived chemotaxin 2)-associated amyloidosis is a type of systemic amyloidosis that is caused by the deposition of amyloid protein composed of leukocyte cell-derived chemotaxin 2 (LECT2) in various organs of the body. LECT2 is a protein produced by the liver and is involved in regulating immune response and inflammation.
ALECT2 amyloidosis typically affects the kidneys and liver, but can also affect other organs such as the spleen and adrenal glands. Symptoms of ALECT2 amyloidosis can vary depending on the affected organs but may include proteinuria (protein in urine), nephrotic syndrome (a kidney disorder characterized by high levels of protein in urine), and hepatomegaly (enlarged liver).
ALECT2 amyloidosis is a rare disease, and little is known about its causes or treatment. Diagnosis of ALECT2 amyloidosis is typically made by a biopsy of the affected organ and confirmed through laboratory analysis of the amyloid protein.