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AMYLOIDOSIS AWARENESS for Patients and Their Support Network, Including Physicians, Nurses and Medical Students

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AMYLOIDOSIS AWARENESS for Patients and Their Support Network, Including Physicians, Nurses and Medical Students AMYLOIDOSIS AWARENESS For patients and their support network, including physicians, nurses and medical students Section Name Here 1 TABLE OF CONTENTS 1 One Minute Overview 1 2 What is Amyloidosis? 2 3 Types of Amyloidosis 7 4 Diagnosis 17 5 Treatments 26 6 Major Amyloidosis Centers 37 Published October 2013. 7 Online Resources 39 This booklet has been made with the guidance of Amyloidosis Support Groups. Special thanks to doctors Morie Gertz, Angela Dispenzieri, Martha Grogan, Shaji Kumar, Nelson Leung, Mathew Maurer, Maria Picken, Janice Wiesman, and Vaishali Sanchorawala. While the information herein is meant to be accurate, the medical sciences are ever advancing. As such, the content of this publication is presented for educational purposes only. It is not intended as medical advice. All decisions regarding medical care should be discussed with a qualified, practicing physician. Illustration artwork © Fairman Studios, LLC. Cover image: Amyloidosis often occurs in middle-age and older individuals, but also in patients in their 30s or 40s, and occasionally even younger. 1. ONE MINUTE OVERVIEW 2. WHAT IS AMYLOIDOSIS? All of the normal proteins in our body are biodegradable Throughout our lifetime, our DNA is coding for the manufac- and recyclable. Amyloidosis is a disease in which abnor- ture of small molecules called proteins. These proteins provide mal proteins (amyloid) are resistant to being broken down. the structure and function for nearly all of life’s biological pro- As a consequence, the amyloid proteins deposit and ac- cesses. Enzymes that facilitate our cells’ chemistry, hormones cumulate in the body’s tissues. If amyloid builds up in the that affect our body’s growth and regulation, and antibodies kidney, heart, liver, gastrointestinal tract or nerves, it causes that form our immune response are all examples of proteins in those organs to function poorly. Thus, the symptoms of action. Just about everything in our bodies – from the color of amyloidosis are associated with the abnormal functioning our eyes, to carrying oxygen in our blood, to whether we can of the organs involved. Typically, patients will have some of digest milk – is determined by the proteins we make. the following symptoms: unexplained weight loss, fatigue, shortness of breath, foamy urine, swelling in the ankles and Once produced within the body, proteins will naturally fold legs, as well as numbness and tingling in the hands and into a particular shape. This natural form of a protein mol- feet. These are manifestations of damage to the underlying ecule is what allows for its specific function. Put simply, organs from the insoluble amyloid protein. Treatments are when proteins are folded properly, they work as they should, designed either to dissolve the amyloid deposits or to inter- and we enjoy relatively good health. When proteins are mis- rupt their production. Left untreated, the disease can be folded, it affects our body’s ability to function, and problems life-threatening. Therefore, early and accurate diagnosis is may arise over time. the key to promoting positive outcomes. Misfolded proteins can be produced because of genetic causes, or because of other factors related to chronic in- flammation or increasing age. Regardless, our bodies are usually capable of identifying and removing these abnormal proteins. In some cases, though, we either produce too much of the abnormal proteins for our body to handle, or we are not able to break down and clean up the proteins at all. Such defects in protein production and processing are as- sociated with many diseases. 1 What is Amyloidosis? 2 Broadly speaking, amyloidosis (pronounced ‘am-uh-loy- doh-sis’) is one class in a growing list of protein folding dis- orders. While there are many distinct types of amyloidosis, in all cases the misfolded proteins, called amyloid (meaning ‘starch-like’), take on a particular shape that makes it diffi- cult for the body to break down. Because of this misfolding, the amyloid proteins bind together to form rigid, linear fibers (or fibrils) that accumulate in our body’s organs and tissues. Depending on where the amyloid builds up, such as in the kidney, heart and nerves, different symptoms and potentially life-threatening conditions become manifest. While amyloidosis has been known since the 19th century, it is only within the last few decades that our understanding of it has matured. Presently, there are over 25 different proteins that have been identified as contributing to amyloidosis (the major forms of which are described in the next section). Ad- ditional types of precursor proteins that can lead to amyloid formation continue to be discovered through ongoing re- search. Certainly, amyloidosis is a rare condition and often over- Amyloid is a starch-like substance caused by the misfolding of proteins. looked. Each year, an estimated 50,000 people worldwide Amyloid binds together into rigid, linear fibers (fibrils) that deposit in the will become afflicted with the disease, with more than 3,000 tissues and organs. people being diagnosed in North America alone. This is about 1/5 of the incidence of multiple myeloma, and of similar incidence to that of Hodgkin’s disease or chronic my- elogenous leukemia. Because of its rarity, medical students 3 What is Amyloidosis? 4 and physicians may not expect to see amyloidosis in their practice. Moreover, because the condition’s nonspecific, ever-worsening symptoms (e.g., being tired or out of breath) may be mistaken for more common problems of lung and cardiovascular disease, it is very likely that the actual preva- lence of amyloidosis is greater than now recognized. It is imperative for clinicians and pathologists to consider amyloidosis as part of their differential diagnosis (discussed in section 4). Given the unique staining and spectroscopic properties of amyloid proteins, it is a simple matter to test for the disease. Early, accurate diagnosis is essential for pa- tients to benefit from new treatments (discussed in section 5) that are available to improve and extend life. Misfolded proteins can be produced because of genetic causes, or because of other factors related to chronic inflammation or increasing age. 5 What is Amyloidosis? 6 3. TYPES OF AMYLOIDOSIS While the condition’s symptoms and treatments depend on the organs affected, the several types of amyloidosis can There are many different proteins in our bodies that can be- be classified according to the precursor protein involved. As come misfolded to produce amyloidosis. The predisposition seen in Table 1 (next page), a convenient naming system is to form abnormal proteins can be inherited from our par- used, such that the prefix “A” refers to amyloid, followed by ents, or even arise from DNA mutations acquired during our an abbreviation for the associated protein. For example, AL lifetime. In some instances, amyloidosis results from chronic designates amyloid derived from light-chain antibodies; AA inflammatory and infectious diseases, or long-term kidney designates serum amyloid A protein; and ATTR designates dialysis. Most diagnosed cases, however, are caused by a amyloid from transthyretin. bone marrow condition that has similarities with multiple myeloma. As new amyloid proteins are characterized, and as our medical understanding deepens, it is possible to discuss the As the amyloid proteins accumulate in our bloodstream, different types of amyloidosis from a wider perspective. Be- they ultimately deposit in organs and tissues. The resulting low is a brief description of AL amyloidosis; AA amyloidosis; amyloid fibrils may impair multiple organ systems or local- familial amyloidosis; senile systemic amyloidosis; as well as ize in one area of the body. Amyloid will deposit most com- ALECT2, dialysis-related, and localized amyloidosis. monly in the kidney, heart and nerves, with the liver, spleen, gastrointestinal tract, and airways also occasionally affect- AL Amyloidosis ed. Amyloid is oftentimes found in the pancreas of people AL (or primary) amyloidosis is the most commonly diag- who develop diabetes as adults. nosed form of the disease, accounting for 85% of all cases in developed countries. The disorder begins in the bone Although the precursor proteins that lead to amyloidosis marrow, the soft tissue that fills the cavities of our bones, come in various shapes and sizes, they all share the same where red and white blood cells are formed. One kind of misfolded structure as amyloid deposits. This unifying white blood cell, called plasma cells, produces antibodies feature of amyloid, wherein a protein’s normal alpha-helical that protect us from infections. These antibody proteins (im- shape misfolds into a beta-pleated sheet, allows for precise munoglobulins) are made up of light and heavy chain mol- and timely diagnosis of the disease (discussed in the next section). 7 Types of Amyloidosis 8 TYPE SOURCE OF AMYLOID SYNDROME (Precursor Protein) AL, AH, Plasma cells in the Primary form of amyloidosis, similar to ALH bone marrow multiple myeloma, affecting the ecules. Normally, our plasma cells produce whole antibod- (Immunoglobulin light kidneys, heart, liver, gastrointestinal or heavy chains, or both) tract, and nerves. ies, and our body breaks down these proteins and recycles them after a short time. In AL, though, too many unas- AA Circulating Secondary to chronic inflammatory inflammatory protein and infectious diseases, affecting the sembled, misfolded light chains are being made. These “free (Serum amyloid A) kidneys and liver. light chains” (and, in rare cases, free heavy chains) cannot ALECT2 White blood cells Clinically resembles AL, affecting the be broken down efficiently. They bind together to form amy- (Leukocyte kidneys and liver. loid fibrils that build up in the extracellular space of organs chemotactic factor 2) and tissues. In this way, the body’s normal functioning is Aβ2M Circulating serum protein Dialysis-related, affecting the joints impaired. Problems typically arise in the kidney, heart, liver, (β2-microglobulin) and tendons. spleen, nerves, intestines, skin, tongue, and blood vessels.
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