DEFINITION GENERALITY

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=95 BGCOLOR="#999999" TEXT="#080000" bgproperties="fixed" background="048005f0ermwup.png"> <div> <FONT SIZE="5" COLOR="#FFFFFF" FACE="Arial" ><B>amyloidosis</B></FONT><B>     </B><B>|     </B><A HREF="index.htm" TARGET="_top" TITLE="amyloidosis"><U><B>home</B></U></A></div> <div> <B>DEFINITION GENERALITY</B>   |   <A HREF="id20.htm" TARGET="_top" TITLE="specificity"><U>specificity</U></A>   |   <A HREF="id21.htm" TARGET="_top" TITLE="chart"><U>chart</U></A>   |   <A HREF="id22.htm" TARGET="_top" TITLE="pictures"><U>pictures</U></A>   |   <A HREF="id23.htm" TARGET="_top" TITLE="Treatment"><U>Treatment</U></A>   |   <A HREF="id17.htm" TARGET="_top" TITLE="Related Links"><U>Related Links</U></A>   |   <A HREF="id18.htm" TARGET="_top" TITLE="Contact Me"><U>Contact Me</U></A></div> <div> </div> </td> </tr><tr> <td valign="top" width=190 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> <B>danil hammoudi.md</B></div> <div> <B><IMG SRC="081e1780.png" border=0 width="225" height="120" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">DR.FREIDLANDER</B></div> <bR> <div> <B>OTHER NAMES FOR AMYLOIDOSIS</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloid Arthropathy of Chronic Hemodialysis Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Abercrombie Syndrome</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloidosis of Familial Mediterranean Fever</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atypical Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cardiopathic Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hereditary Nephropathic Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lichen Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Macular Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neuropathic Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paramyeloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pericollagen Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Primary Cutaneous Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Primary Nonhereditary Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Secondary Generalized Amyloidosis</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f0bf000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Waxy Disease</B></div> <bR> <bR> <bR> </td> <td valign="top" height=385 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> DEFINITION GENERALITY</div> <div> Amyloidosis was first described in the 19th Century.</div> <bR> <div>  Amyloidosis is now known to be a group of diseases in which one or more organ systems in the body accumulates protein deposits.</div> <bR> <div> abnormal protein that may be deposited in any of your body's tissues or organs. </div> <div> This abnormal protein comes from <FONT SIZE="3" COLOR="#6666FF" FACE="Arial" ><B><U>cells in the bone marrow.</U></B></FONT> </div> <bR> <div> <B>disabling or life threatening.</B> </div> <bR> <bR> <div> The disease known as amyloidosis (pronounced am-i-loy-do'-sis) results when enough amyloid protein builds up in one or more organs to cause the organ(s) to malfunction.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The heart, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">kidneys, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nervous system </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">spleen</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">adrenal</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">gastro-intestinal tract are most often affected. </B></div> <bR> <div> the site of deposition depend on the type of amyloidosis primary or secondary.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloidosis is a bone marrow disease. </div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> bone marrow makes protective antibodies. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> After they have served their function, these antibodies are broken down and recycled by the system.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the  amyloidosis, cells in the bone marrow produce antibodies that cannot be broken down. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These antibodies then begin to build up in the bloodstream.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Ultimately, they leave the bloodstream and can deposit in your tissues as amyloid. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">amyloid is a hyalin substance that stains specifically with congo red, when examined with ME is found to be composed of fibers lacking periodicity [see specificity chapter]</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">amyloid is produced by the reticulum endothelial system  and is deposited extracellularily.</div> <bR> <bR> <bR> <div> <B><U>recognition in 3 categories:</U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">typical amyloidosis</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">slpeen</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">kidney</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">liver</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">adrenal</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">intestinal mucosa [rectal bipsy for diag]</div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">atypical amyloidosis</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">any organ in addition to those mentioned   [amyloidosis of the age affecting more the heart , 3% over 70 years old]</div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">tumor forming amyloidosis</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nodules of infiltrates by plasma cells may occurs [tongue]</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">tumor like deposits [pancreas islets and c cell thyroid tumors [calcitonin producing cells] </div> <bR> <div> <I><B><U> There are three major etiologic types, all very different from each other.</U></B></I> </div> <bR> <bR> <div> <B><U>1. Primary Amyloidosis</U></B><B><U> </U></B></div> <bR> <div> <B><U>familial mediterranean fever = typical amyloidosis</U></B></div> <div> <B><U>neuropathic amyloidosis = atypical amyloidosis</U></B></div> <bR> <div> <I><B>Primary amyloidosis is a plasma cell disorder and occasionally occurs with multiple myeloma.</B></I><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> This is the most common type of amyloidosis in the United States and is usually treated (conventionally) with chemotherapy. </div> <div> Primary amyloid is not associated with any other diseases. </div> <div> In primary amyloidosis, the organs most often involved include:</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> the heart, kidneys, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nervous system, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> gastrointestinal tract. </div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloid deposits in these organs cause:</div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> shortness of breath,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> fatigue, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">edema (swelling of ankles and legs), </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dizziness upon standing,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> a feeling of fullness in the stomach (especially after eating),</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> diarrhea, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">weight loss, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">enlarged tongue,</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> numbness of the legs and arms, </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and protein in the urine. </B></I></div> <bR> <div> <I><B><U><IMG SRC="06484450.png" border=0 width="388" height="325" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></I></div> <bR> <bR> <bR> <bR> <div> <B><U>2. Secondary Amyloidosis</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <div> Secondary amyloid is caused by a chronic infection or inflammatory disease. </div> <div> tuberculosis is present in 50% of the cases of amyloidosis</div> <div> osteomyelitis 12% </div> <div> chronic lung infection 10% </div> <div> other chronic infections 12% = hyperimmunization</div> <div> primary chronic polyarthritis 20% of cases show amyloidosis</div> <div> Treatment of the underlying chronic infection or inflammatory disease can slow down or stop the progression of this type of amyloid. </div> <div> In secondary amyloidosis, symptoms caused by the underlying chronic infection or inflammatory disease are complicated by the development of amyloid deposits in the kidney. </div> <div> <B>This may cause protein in the urine, edema, and fatigue </B></div> <bR> <bR> <bR> <bR> <div> <B><U>3. Hereditary Amyloidosis</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> Familial amyloid is the only type of amyloidosis that is inherited. </div> <div> It is rare and is found in families of nearly every ethnic background. </div> <div> <I><B>In hereditary amyloidosis, the nervous system and gastrointestinal tract are often involved.</B></I> </div> <div> <B>This can cause numbness and tingling in the arms and legs, dizziness upon standing, and diarrhea.</B> </div> <bR> <div> Families have their own pattern of organ involvement and symptoms.</div> <div>  The transmission is autosomal dominant, which means that if you have this type of amyloidosis each of your children has a 50% chance of inheriting the disease.</div> <div>  If your child does not inherit the gene, he/she cannot pass it on to future generations. </div> <bR> <bR> <bR> <bR> <div> <B><U>4. Other types of amyloidosis</U></B><B><U> </U></B></div> <bR> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >include</FONT><B> localized amyloid, b</B><FONT SIZE="1" COLOR="#3300FF" FACE="Arial" ><B>2</B></FONT><B> microglobulin amyloid, and Alzheimer's disease</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" >. </FONT></div> <bR> <div> Localized types of amyloidosis are associated with hormones, proteins, aging, and specific areas of the body, and are not found with systemic involvment. </div> <div> The type of amyloidosis which is due to the b<FONT SIZE="1" COLOR="#000000" FACE="Arial" >2</FONT> microglobulin protein may affect people who have been on dialysis for a significant length of time.</div> <div>  In Alzheimer's disease, the amyloid protein in the brain is called the b-amyloid protein. </div> <div> Amyloidosis can only be diagnosed by a positive biopsy; that is, an identification of the amyloid deposits in a piece of tissue. </div> <bR> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloidosis is rare, affecting about 8 persons per million annually. Its cause is not known. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It can affect anyone, but the majority of people who get amyloidosis are over the age of 40. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Primary amyloidosis is not contagious or inherited.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It is not known how many people have this disease. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">About 10 percent of patients who have multiple myeloma (a form of bone marrow cancer), develop amyloidosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although amyloid is an abnormal protein, diet and the amount of protein you eat play no role in the development of the disease. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Also, there is no recognized link between amyloidosis and stress or occupation. </div> <bR> <bR> <bR> <div> <B><U>ACQUIRED AMYLOIDOSIS</U></B><B><U> </U></B></div> <bR> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Protein </U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">AL: Immunoglobulin light chains; <FONT SIZE="3" COLOR="#000000" FACE="symbol" >k</FONT> or <FONT SIZE="3" COLOR="#000000" FACE="symbol" >l</FONT> </div> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Clinical</U></B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most common in middle aged males </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Associated disorders </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paraproteinemia (<U>M-protein)</U> </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In 90% when serum & urine tested by immunofixation </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most common in nephrotic syndrome </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Least common in polyneuropathy </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Light chain in 1/3 </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Intact immunoglobulin in 2/3 </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">l<FONT SIZE="3" COLOR="#000000" FACE="Arial" > light chains: AL type </FONT></div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">k<FONT SIZE="3" COLOR="#000000" FACE="Arial" > light chains: Multiple myeloma; MGUS </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Multiple myeloma : May present 10-81 months after diagnosis of AL </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polyneuropathy: Occurs in 20% of patients with light chain amyloid </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Distal; Symmetric </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Predominantly sensory </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pain & temperature loss most prominent</div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Distal weakness may develop later </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Autonomic </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Orthostatic hypotension </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypoactive pupils </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypohydrosis </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Bladder dysfunction </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Impotence </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Carpal tunnel syndrome in 25% </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Myopathy</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Systemic features </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Purpura: Periorbital </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Submandibular swelling </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cardiac </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Renal: Nephrotic syndrome </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Muscle enlargement</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > ± weakness </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Gastrointestinal: Diarrhea </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Anemia associated with multiple myeloma </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloidoma</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Laboratory </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CSF: Protein mildly elevated </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Electrodiagnostic: Axonal neuropathy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Biopsy: Axonal loss; Amyloid </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Prognosis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Gradual progression </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Survival of 1 to 10 years depending on organ involvement </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Shortest survival with cardiac (< 1 year) & renal dysfunction</div> <bR> <bR> <bR> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="16" ALIGN="bottom" HSPACE="0" VSPACE="0"><A NAME="hereditary"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>HEREDITARY PNS AMYLOIDOSIS</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mutations in serum proteins that can form <FONT SIZE="3" COLOR="#000000" FACE="symbol" >b</FONT>-pleated sheets</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Protein forming the amyloid is identified by immunocytochemistry</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Liver transplantation may be effective therapy</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"><A NAME="transthyretin"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ATTR: Transthyretin (Prealbumin)</U></B><B><U> </U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f0ff00ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">l<FONT SIZE="3" COLOR="#000000" FACE="Arial" > Chromosome 18q11.2-q12.1; Dominant </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ATTR gene </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">4 exons: Exon 1 codes for signal peptide </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mutations </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">General locations </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Exon 1: Only 1 mutation (Val20Ile); Not in signal peptide </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">> 70 in other 3 exons </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Specific mutations: Variable clinical presentation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Val30Met: Most common; Onset 25 to 65 years; Small fiber & autonomic <FONT SIZE="3" COLOR="#000000" FACE="Symbol" >D</FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Val28Met: 7th decade onset neuropathy with impotence; No FH </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Database: <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>HGMD</U></FONT> </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Types: Most are missense point mutations </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ATTR Protein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">127 amino acids </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Present in plasma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Binds: Thyroxine (20%); Retinol binding protein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Clinical syndromes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Heterogeneous, with some relation to: </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Point mutation & Ethnic background </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Signs include: </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Peripheral nerve </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polyneuropathy: Sensory, Autonomic, ± Motor </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Carpal tunnel syndrome</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Systemic: Cardiomyopathy, Vitreous opacities, Renal failure </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Rare CNS </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Glycine 18: Meningocerebrovascular syndrome sparing eyes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Glycine 30: Oculoleptomeningeal syndrome </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ile107Val: Autonomic; Carpal tunnel; CNS; Multisystem (Cardiomyopathy; Lung; Joint; Angiopathy) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">General signs: Hearing loss; Migraine; Dementia; <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Cerebellar</U></FONT>; Seizures; Stroke; <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Myelopathy</U></FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Onset 17-78 years </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Earlier: Portuguese; Japanese endemic Val30Met foci </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Later: Swedish; Sporadic Japanese Val30Met patients </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? Anticipation: Not explained by triplet repeats </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Homozygotes & heterzygotes with same clinical manifestations </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Penetrance: Variable: 30% to 95% </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="16" ALIGN="bottom" HSPACE="0" VSPACE="0"><A NAME="fap1"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FAP I </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Presentation: Generalized Autonomic & Sensory Polyneuropathy </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Onset: Legs </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Painful dysesthesias </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most common point mutation: Val30Met </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Onset: 20 to 80 years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Later: Sporadic Japanese cases; Swedish endemic foci </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Earlier: Japanese & Portugese endemic foci </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Penetrance </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">High: Endemic Japanese foci </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Low: Scattered, sporadic cases; Swedish endemic foci </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Male > Female: Especially in late onset sporadic cases </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Weakness: Distal; Legs > Arms </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sensory loss </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Early onset: Pain & Temperature loss most prominent </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Late onset: Distal; Symmetric; All modalities; Paresthesias </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tendon reflexes: Reduced or Absent </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Autonomic failure </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Severe in early onset patients </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mild in late onset patients </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Progression: Death in 7 to 10 years </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CSF protein: Moderately <FONT SIZE="3" COLOR="#000000" FACE="Wingdings" >é</FONT> in 20% </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sural nerve biopsy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Axonal loss: Myelinated axons especially in older onset patients </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Amyloid: Most prominent in sympathetic ganglia, dorsal root ganglia & proximal nerve trunks </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Treatment: Liver transplantation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Also > 23 other mutation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">"Portuguese, Swedish & Japanese" types </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FAP II </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Onset: </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Upper extremities, esp carpal tunnel syndrome </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">5th decade </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most common mutation: Ser77Tyr </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Onset </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">51 to 67 years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Carpal tunnel syndrome: May be only manifestation for 1 to 2 decades </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Generalized polyneuropathy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pain & Paresthesias </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Weakness: Symmetric; May become severe </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Restrictive cardiomyopathy: Arrhythmia; Cardiac insufficiency </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Autonomic: Intestinal malabsorption; Hypotnesion </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">No renal or ocular involvement </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Progression </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Variable: Some stable; Others rapidly progressive </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Survival high </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Severe disability may develop </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Treatment: Liver transplantation for disabled < 65 years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">> 6 other point mutations </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">"Indiana & Maryland " types </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other point mutations present with Cardiomyopathy or Renal disease </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cardiomyopathy: Val122Ile mutation </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Common in black population </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Late onset: > 60 years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="16" ALIGN="bottom" HSPACE="0" VSPACE="0"><A NAME="apo1"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">AApoA1: Apolipoprotein A-1 </B>(FAP III; "Iowa" type) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f0ff00ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">l<FONT SIZE="3" COLOR="#000000" FACE="Arial" > Chromosome 11q23.3; Dominant </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Gene </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neuropathic amyloid: Point mutation Gly26Arg </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other amyloid mutations: Trp50Arg; Insertions & deletions </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Protein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Transports cholesterol from tissues to liver </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Major plasma & chylomicron protein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Clinical features (Iowa type): Similar to <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>FAP I</U></FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Polyneuropathy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nephropathy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Gastric Ulcer </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Other non-neuropathic amyloid syndromes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hepatic failure </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cardiac ± Cutaneous: Leu90Pro; Arg173Pro; Leu174Ser </div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="16" ALIGN="bottom" HSPACE="0" VSPACE="0"><A NAME="gelsolin"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">AGel: Gelsolin</B> (FAP IV; "Finnish" (also Japanese) type ) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f0ff00ff00.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">l<FONT SIZE="3" COLOR="#000000" FACE="Arial" > Point mutations amino acid 187; Chromosome 9q32-q34; Dominant </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Protein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Binds to: </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Actin: barbed end of filaments; Prevents monomer exchange</div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fibronectin </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Intracellular: Muscle; Phagocytes; Fibroblasts; Platelets </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Clinical features </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Onset: 4th decade </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cranial Neuropathies </div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Facial paresis (Upper)</div> <div> <IMG BORDER="0" SRC="Wing0a73006f00f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Also: V; XII; VIII </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Corneal lattice dystrophy: Also see Lattice corneal dystrophy IIIA </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sensory neuropathy (Vibration loss) ± autonomic </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Skin: Laxity </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">No cardiac involvement </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Homozygotes: Rapidly progressive disease & Renal failure</div> <bR> <bR> <div>  <A NAME="3"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> <B><U>What are the symptoms of amyloidosis in general?</U></B></div> <div> Symptoms of amyloidosis depend on the organs it affects. The wide range of symptoms often makes amyloidosis difficult to diagnose. You may have no symptoms. Symptoms can include: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Swelling of ankles and legs </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Weakness </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Weight loss </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Shortness of breath </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Numbness or tingling in the hands or feet </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diarrhea </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Severe fatigue </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Enlarged tongue </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Feeling of fullness after eating smaller amounts of food than usual </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Dizziness upon standing </div> <bR> <bR> <div>  <A NAME="7"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> <B><U>How is amyloidosis diagnosed?</U></B></div> <div> Physical examination is necessary to find out if your organs are functioning properly. </div> <div> Blood, urine and bone marrow tests may also be done.</div> <div>  A small tissue sample (biopsy) may be taken from your rectum, abdominal fat or bone marrow to determine if you have amyloidosis.</div> <div>   Occasionally, samples are taken from the liver, nerve, heart or kidney. </div> <div>  </div> <div> Blood or urine tests can detect the protein, but only bone marrow tests or other small samples of tissue can positively establish the diagnosis of amyloidosis</div> <bR> <bR> </td> </tr></table></body>