FABRY DISEASE

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <script> cookie_name="pop1"; cook_value="1!!1260339465"; cook_expires="Wed, 09 Dec 2009 06:18:45 GMT"; document.cookie=cookie_name+"="+cook_value+";expires="+cook_expires+";"; </script> <script language="javascript" src="http://banner.0catch.com/cgi-bin/popup_mainsite.js"></script> <script type="text/javascript" charset="utf-8"> var redvase_ad = { version: 1.5 }; redvase_ad.publisher = 'zerocatch'; redvase_ad.kind = 'popunders'; redvase_ad.content = 'pop'; redvase_ad.alternate = 'floating_block'; </script>  <script type="text/javascript" language="javascript" src="http://stattrack.0catch.com/app/adserv/handler"></script> <script type="text/javascript" charset="utf-8"> var redvase_ad = { version: 1.5 }; redvase_ad.publisher = 'zerocatch'; redvase_ad.kind = 'zerocatch_tips_tricks_newsletter'; redvase_ad.content = 'creative' </script> <script src="http://redvase.bravenet.com/javascripts/redvase.js" type="text/javascript" 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TARGET="_top" TITLE="New Born Assessment "><U><B>New Born Assessment </B></U></A></div> <div> <A HREF="id38.htm" TARGET="_top" TITLE="laryngomalacia"><U><B>laryngomalacia</B></U></A></div> <div> <A HREF="id39.htm" TARGET="_top" TITLE="CRANIOSYNOSTOSIS "><U><B>CRANIOSYNOSTOSIS </B></U></A></div> <div> <A HREF="id40.htm" TARGET="_top" TITLE="DANDYWALKER MALFORMATION "><U><B>DANDY-WALKER MALFORMATION </B></U></A></div> <div> <A HREF="id41.htm" TARGET="_top" TITLE="DEJERINESOTTAS DISEASE "><U><B>DEJERINE-SOTTAS DISEASE </B></U></A></div> <div> <A HREF="id42.htm" TARGET="_top" TITLE="DOWN SYNDROME "><U><B>DOWN SYNDROME </B></U></A></div> <div> <A HREF="id43.htm" TARGET="_top" TITLE="Respiratory Syncytial Virus (RSV)"><U><B>Respiratory Syncytial Virus (RSV)</B></U></A></div> <div> <B>FABRY DISEASE </B></div> <div> <A HREF="id45.htm" TARGET="_top" TITLE="PRADERWILLI SYNDROME "><U><B>PRADER-WILLI SYNDROME </B></U></A></div> <div> <A HREF="id37.htm" TARGET="_top" TITLE="new born fun"><U><B>new born fun</B></U></A></div> <div> <A HREF="id46.htm" TARGET="_top" TITLE="RETT SYNDROME "><U><B>RETT SYNDROME </B></U></A></div> <div> <A HREF="id47.htm" TARGET="_top" TITLE="Alexander Disease"><U><B>Alexander Disease</B></U></A></div> <div> <A HREF="id49.htm" TARGET="_top" TITLE="leukemia"><U><B>leukemia</B></U></A></div> <div> <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U><B>Contact Me</B></U></A></div> </td> <td valign="top" height=370 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> FABRY DISEASE </div> <div> <B><U>DEFINITION:</U></B></div> <div> A lysosomal storage disorder characterized by the accumulation of lipid (glycosphingolipid) in peripheral tissues resulting in the triad of acroparesthesia, angiokeratomas, and corneal opacities. </div> <div> <B><U>EPIDEMIOLOGY:</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">incidence: over 300 cases reported </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">age of onset: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">late childhood -> adolescence </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">risk factors: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">familial - x-linked recessive with complete penetrance but variable phenotype </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">chrom.#: Xq22 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">gene: alpha-galactosidase A </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">M only </div> <div> <B><U>PATHOGENESIS:</U></B></div> <div> 1. Background</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">alpha-galactosidase A catalyzes the conversion of trihexosylceramide to dihexosylceramide </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">the alpha-galactosidase gene has been cloned </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">disease originally described by Fabry in 1898 </div> <div> 2. Genetic Defect</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">genetic defect -> deficiency of alpha-galactosidase A activity -> accumulation of three glycosphingolipids in peripheral tissues: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">trihexosylceramide - in the endothelium of blood vessels and is the major cause of pathology </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">digalactosylceramide - accumulate in the heart & kidneys </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">blood group B-1 - increase the progression of the disglycolipid ease in those with type B blood group </div> <div> <B><U>CLINICAL FEATURES:</U></B></div> <div> 1. Neurological Manifestations</div> <div> 1. Peripheral Nervous System</div> <div> 1. Acroparesthesia</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">burning pain crises of the extremities </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">onset in childhood </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may be the initial manifestation of the disease </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">crises </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">periodic and excruciating </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may become more frequent and severe with age then lessen in the 2nd or 3rd decades </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">precipitated by heat, cold, exercise, humidity, fever, and/or fatigue </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">last from several hours to days </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">usually associated with a low-grade fever and elevated ESR </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">burning or tingling sensation beginning in the fingers and toes and spreading proximally </div> <div> 2. Central Nervous System</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cerebral vascular disease with ischemia and infarction in cortical and brainstem areas -> strokes, seizures, person-ality changes, and hemiplegia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">no mental retardation </div> <div> 2. Cutaneous Manifestations</div> <div> 1. Angiokeratomas</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">small dark purple-blue telangiectasia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may appear in childhood but usually not noted until after </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">10 years of age </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">most dense between the umbilicus and knees with propensity for umbilicus and buttocks </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">progressive increase in the size and number with age </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">do not blanch with pressure </div> <div> 2. Others</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypohidrosis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lymphedema of the legs </div> <div> 3. Ocular Manifestations</div> <div> 1. Cornea</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">linear/whorling opacities originating from a central vortex </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">also have lenticular opacities </div> <div> 2. Lens</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cataracts </div> <div> 3. Retina</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dilated and tortuous retinal vessels with aneurysmal dila-tation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">papilledema +/- hypertensive changes </div> <div> 4. Respiratory Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">chronic airflow obstruction </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dyspnea </div> <div> 5. Cardiac Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">conduction defects </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypertension </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ischemic heart attacks </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mitral valve insufficiency </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">thromboses </div> <div> 6. Gastrointestinal Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">abdominal and/or flank pain </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">diarrhea </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hepatomegaly </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nausea and vomiting </div> <div> 7. Renal Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">proteinuria eventually leading to end stage renal failure (ESRF) between the 2nd and 4th decades </div> <div> 8. Musculoskeletal Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">permanent deformity of the distal interphalangeal joint of the fingers </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">avascular necrosis of the head of the femur or talus with limp, knee pain, and/or hip pain </div> <div> 9. Endocrine Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">short stature </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">delayed puberty </div> <div> <B><U>INVESTIGATIONS:</U></B></div> <div> 1. Diagnosis</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">deficiency of alpha-galactosidase activity in WBC's or cultured skin fibroblasts </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mild corneal opacities in 80% of obligate heterozygotes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">prenatal </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">deficiency of alpha-galactosidase activity in cultured chorionic villi or amniocytes </div> <div> 2. Serum</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">elevated trihexosylceramide </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mild microcytic hypochromic anemia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">abnormal renal function (ESRF) </div> <div> 3. Urine</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">elevated trihexosylceramide - WBC's and casts </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lipid inclusions with characteristic - isosthenuria birefringent "Maltese crosses" </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">proteinuria +/- hematuria </div> <div> 4. EKG</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">left ventricular hypertrophy - T-wave inversion </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ST segmental changes - short PR interval </div> <div> 5. Pathology</div> <div> 1. Biopsy</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lipid accumulation in: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">kidneys - epithelial & endothelial cells of glomeruli and tubules </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">airways - airway epithelium </div> <div> <B><U>MANAGEMENT:</U></B></div> <div> 1. Supportive</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">no treatment available for disease </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">multidisciplinary approach </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paediatrics, Neurology, Dermatology, Ophthalmology, Cardio-logy, Nephrology, Endocrinology </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">painful crises treated with low dose diphenylhydantoin or carbamazepine </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">renal transplant for ESRF </div> <div> 2. Prognosis</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mean age of survival is 42 years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">death from ESRF or vascular disease of the heart or CNS </div> <bR> </td> </tr></table></body>