Difficult concepts are clarified, using simple diagrams to explain the link between pathology and clinical presentation. [books.google.com]

PDF Merrill Benson and Isis = Presentation PDF Teresa M Kruisselbrink, CGC Presentation PDF A.K. [amyloidosissupport.org]

Clinical description FAP is clinically heterogeneous, with the clinical presentation depending on the genotype and geographic origin. FAP usually presents as a length-dependent sensory polyneuropathy with autonomic disturbances. [orpha.net]

Diagnosis is based on clinical presentation, amyloid deposition on tissue biopsy, and the diagnostic hallmark TTR mutation on genetic testing. [ng.neurology.org]

The clinical presentation is very varied because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are weakness and dyspnoea. [patient.info]

• Swelling

  For heart or kidney problems, you may want to: Cut back on salt, to help keep swelling in check. Wear elastic stockings, to help blood flow back up from your legs. Raise your legs when sitting or lying down, also to control swelling. [webmd.com]

  Support stockings may be recommended for patients with leg edema (swelling). [ttrstudy.com]

  Fluid retention causing swelling of the legs and edema Shortness of breath Light-headedness or dizziness Hoarseness of voice Tongue may be enlarged and affected by plaques, blood spots or blisters Related Stories Recent advances in non-viral nano-vector [news-medical.net]

  This can lead to fluid build- up, causing leg swelling (oedema) and breathlessness due to fluid in the lungs. This problem is exacerbated if the patient drinks too much fluid. [amyloidosis.org.uk]

  Signs and symptoms of amyloidosis may include: Swelling of your ankles and legs Severe fatigue and weakness Shortness of breath Numbness, tingling or pain in your hands or feet, especially pain in your wrist (carpal tunnel syndrome) Diarrhea, possibly [mayoclinic.org]

• Congestive Heart Failure

  Supportive Treat symptoms - eg, diuretics for kidney failure, erythropoietin for anaemia. Congestive heart failure may respond to diuretics, but larger doses are often required as the disease progresses. [patient.info]

  Cardiac involvement is a leading cause of morbidity and mortality, especially in AL amyloidosis. 1 Once congestive heart failure occurs in AL amyloidosis, median survival is less than 6 months if left untreated. [dovepress.com]

  These insoluble fibrils accumulate in the myocardium and result in diastolic dysfunction, restrictive cardiomyopathy, and eventual congestive heart failure (Figure 1). [pharmaceuticalintelligence.com]

  Congestive heart failure and atrial fibrillation are the most common symptoms. The term “arrhythmia” refers to changes in the normal electrical impulses that cause the heart to beat. [amyloidosis.org]

• Nausea

  Patients may experience painful paresthesias (unusual sensations), numbness and balance difficulties due to sensory dysfunction and persistent nausea, vomiting, diarrhea, constipation, incontinence, sweating abnormalities or sexual dysfunction due to [hopkinsmedicine.org]

  If there is vomiting and diarrhea, careful administration of intravenous fluids and anti‑nausea drugs may be necessary. [ttrstudy.com]

  Intravenous fluids and anti‑nausea drugs may be necessary, but it is important to avoid fluid overload if there is heart disease. [amyloidosis.org.uk]

  The clinical manifestations of autonomic disorders are nonspecific and symptoms can include nausea, vomiting, early satiety, bloating, constipation, diarrhea, postural lightheadedness, and erectile dysfunction. [dovepress.com]

  Other gastrointestinal dysfunctions may require treatment for symptoms that include poor nutritional health, diarrhea or constipation, and nausea or vomiting. [amyloidosis.org]

• Vomiting

  Patients may experience painful paresthesias (unusual sensations), numbness and balance difficulties due to sensory dysfunction and persistent nausea, vomiting, diarrhea, constipation, incontinence, sweating abnormalities or sexual dysfunction due to [hopkinsmedicine.org]

  If there is vomiting and diarrhea, careful administration of intravenous fluids and anti‑nausea drugs may be necessary. [ttrstudy.com]

  The clinical manifestations of autonomic disorders are nonspecific and symptoms can include nausea, vomiting, early satiety, bloating, constipation, diarrhea, postural lightheadedness, and erectile dysfunction. [dovepress.com]

  Care should be taken to avoid dehydration if there is vomiting and diarrhoea. Intravenous fluids and anti‑nausea drugs may be necessary, but it is important to avoid fluid overload if there is heart disease. [amyloidosis.org.uk]

  Other gastrointestinal dysfunctions may require treatment for symptoms that include poor nutritional health, diarrhea or constipation, and nausea or vomiting. [amyloidosis.org]

• Heart Failure

  failure. 1 Ando Y et al. [thaos.net]

  Study of Family Members The father of the subject had died at age 62 from heart failure. Two of his brothers had died at 63 years of age after progressive heart failure (one due to sudden death). [revespcardiol.org]

  Myocardial amyloidosis is the most common cause of death, primarily due to arrhythmias or intractable heart failure. [patient.info]

  The patients often have a long period of a certain organ involved before systemic multiorgan involvement or heart failure has already developed. [dovepress.com]

  In ATTR amyloidosis this may include: Heart disease treatment ATTR amyloid deposits in the heart cause the heart to stiffen which can lead to symptoms of heart failure. Patients can benefit from supportive treatment measures for heart failure. [amyloidosis.org.uk]

• Heart Disease

  White symbols: Without heart disease. Symbols with dot: Carriers without heart disease. Symbols with N: Noncarriers. Symbols with strike-through: Dead. Arrow: Index patient. [revespcardiol.org]

  disease (restrictive cardiomyopathy): Amyloid deposits in the heart cause stiffening and thickening of the heart muscle, so the heart cannot pump the blood around the body as efficiently as usual. [ttrstudy.com]

  In addition, affected individuals may have hepatomegaly, chronic kidney disease or heart disease such as cardiomyopathy. However, in some people, the disease is very mild and causes no apparent symptoms or signs. [ivami.com]

  Congestive heart failure may respond to diuretics, but larger doses are often required as the disease progresses. [patient.info]

  Amyloid heart disease. Progress in Cardiovascular Diseases. 2010;52:347-361. Comenzo RL. How I treat amyloidosis. Blood 2009;114:3147-57 Palladini G, Merlini G. Current treatment of AL amyloidosis. Haematologica 2009; 94:1044-1048. Dember L. [rarediseases.org]

• Hepatomegaly

  Cardiac amyloidosis causes an infiltrative restrictive cardiomyopathy leading to progressive heart failure. [ 8 ] Marked hepatomegaly with kidney disease: Hepatic amyloid disease produces hepatomegaly, but rarely jaundice. [patient.info]

  In addition, affected individuals may have hepatomegaly, chronic kidney disease or heart disease such as cardiomyopathy. However, in some people, the disease is very mild and causes no apparent symptoms or signs. [ivami.com]

  Significant jugular venous distention, moderate hepatomegaly, and lower extremity edema were noted. A neurological examination revealed weakness and muscular atrophy in the bilateral tibialis anterior and gastrocnemius. [dovepress.com]

  Clinical Synopsis: GI: Hepatomegaly; Cholestasis; Splenomegaly GU: Nephropathy with hematuria; Nephrotic syndrome; Uremia Endocrine: Hypertension Skin: Pitting edema; Petechial skin rash Neuro: Nonneuropathic Misc: Chronic weakness Lab: Generalized amyloid [genome.jp]

  Patients with cardiac deposition typically present with the following typical symptoms of chronic heart failure (CHF): Symptoms suggestive of right-sided CHF (ie, dyspnea on exertion, peripheral edema, hepatomegaly, ascites, and elevated jugular venous [emedicine.medscape.com]

• Macroglossia

  Goyal, Tahseen Mozaffar First published July 30, 2015, DOI: https://doi.org/10.1212/NXG.0000000000000018 Abstract Objective: Macroglossia is a well-known feature of amyloidosis; however, tongue atrophy and fasciculations are rarely seen and can lead to [ng.neurology.org]

  Macroglossia, which is common in primary and myeloma-related amyloidoses. Skin lesions: Spontaneous periorbital purpura - racoon eye sign. [patient.info]

• Hyperactivity

  Hyperactive electrogenic sodium-potassium pump is a common phenomenon during the post-ischemic state [ 32 ]. [journals.plos.org]

Imaging studies Radiolabeled P-component scanning Cardiac imaging (eg, 2-dimensional echocardiography, electrocardiography, or both; CT scanning; nuclear scintigraphy, cardiac MRI) See Workup for more detail. [emedicine.medscape.com]

Following this workup the patient should undergo a DNA analysis and tissue biopsy (Table 1 ), although the uneven distribution of amyloid fibrils may yield false-negative results. [ojrd.biomedcentral.com]

Management and treatment Management of FAP should be multidisciplinary, involving a neurologist, geneticist, cardiologist and liver surgeon. [orpha.net]

Continued Treatment Treatment of TTR-FAP depends on your symptoms and how far your condition has developed. The goal of some treatment is to ease the symptoms that are caused when too much amyloid gathers in your organs. [webmd.com]

A summary of the methods used to achieve a TTR-FAP diagnosis is presented, as well as a review of available treatments and recommendations for treatment according to disease status. [pharmaceuticalintelligence.com]

An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant. 2001;28:637-42. [rarediseases.org]

Amyloidosis associated with multiple myeloma has the poorest prognosis, and death within one year is common. All forms of renal amyloidosis have a poor prognosis, but patients may remain stable and even improve with supportive therapy. [patient.info]

Diagnosis - Hereditary ATTR amyloidosis Prognosis - Hereditary ATTR amyloidosis Not supplied. Treatment - Hereditary ATTR amyloidosis Resources - Hereditary ATTR amyloidosis [checkorphan.org]

Prognosis FAP is a severe and disabling disease. Severe cardiac, renal and ocular manifestations may develop. [orpha.net]

Prognosis of patients with primary systemic amyloidosis who present with dominant neuropathy. Am J Med. 1998;104(3):232–237. 8. Koike H, Hashimoto R, Tomita M, et al. [dovepress.com]

Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J Am Coll Cardiol. 2015;66:2451-2466. Mahmoud S, Palladini G, Sanchorawala V, Wechalekar A. Update on treatment of light chain amyloidosis. Haematologica. 2014;99:209-221. [rarediseases.org]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Familial amyloid neuropathy: Unusual etiology in clinical practice. [neurologyindia.com]

Cornea. 2001 Nov; 20(8): 850-2 Babalola,-O-E; Murdoch,-I-E Corneal changes of uncertain etiology in mesoendemic onchocercal communities of Northern Nigeria. [malattierare.regione.veneto.it]

Etiology FAP is transmitted as an autosomal dominant trait and is caused by mutations in the TTR gene (18q12.1). [orpha.net]

They can also be differentiated according to their etiology, secondary (caused by another disease), or primary (cause unknown). Primary amyloidosis generally affect nerves, skin, tongue, joint, heart and liver. [ivami.com]

[…] erythematosus 809 7 857 organic solvents and smoking 903 disease 921 5 995 interstitial disease 1019 The development of the kidney 1050 J Stewart Cameron 1059 malignancy of the kidney 1089 Seppo Vainio 1091 8 1093 parenchymal disease 1361 and J F E Mann 1399 Epidemiology [books.google.com]

Summary Epidemiology The prevalence worldwide is unknown, but the prevalence in the general population in Japan has recently been estimated at around 1 per million. [orpha.net]

Sousa A, Coelho T, Barros J, Sequeiros J: Genetic epidemiology of familial amyloidotic polyneuropathy (FAP)-type I in Póvoa do Varzim and Vila do Conde (north of Portugal). Am J Med Genet 1995;60:512-521. [karger.com]

Epidemiology Amyloidosis is a rare disease. [patient.info]

There are major introductory sections on the scientific basis of disease; and in the system-based clinical sections genetic predisposition, pathophysiology, pathogenesis, molecular mechanisms, and cell biology are covered in depth for all significant [books.google.com]

Islet amyloid and type 2 diabetes; from molecular misfolding to islet pathophysiology. Biochim Biophys Acta. 2001;1537:179-203. Sanchorawala V, Wright DG, Seldin DC, et al. [rarediseases.org]

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test The amyloidoses are a group of diseases that result from the abnormal deposition of amyloid in various tissues of the body. [mayomedicallaboratories.com]

The marked increase of refractoriness at short-width stimulus suggests a defect in sodium current which may represent an early, pre-symptomatic pathophysiological change in TTR-FAP. [journals.plos.org]

The disease has no effective therapy and the mechanisms responsible for pathophysiology are not well understood. Mutations linked to familial ALS have been helpful in exploring the processes that cause the disease. [bitanlab.neurology.ucla.edu]

The purpose of this study is to determine if diflunisal can prevent progressive lower leg nerve damage in patients with familial amyloidosis polyneuropathy. [clinicaltrials.gov]

It gives compreensive coverage of the epidemiology, aetiology, and mechanism of disease, as well as clear, unambiguous coverage of the diagnosis, practical management and prevention of the entire spectrum of medical disorders. [books.google.com]

[…] amyloidosis hATTR amyloidosis is caused by a mutation in the transthyretin (TTR) gene that results in misfolded TTR proteins accumulating as amyloid fibrils in multiple tissues in the body, including the nerves, heart, and gastrointestinal tract. 2,4,5 Prevention [checkorphan.org]

Treatment Treatment of amyloid neuropathies is directed at both preventing further deposition of amyloid in peripheral nerves and treating painful symptoms. [hopkinsmedicine.org]

Screening and prevention of colorectal cancer Source: Finnish Medical Society Duodecim This article is freely available only to users in the UK. [evidence.nhs.uk]