AMLCIDCSIS

Amyloldosls ls a dlsorder of proLeln meLabollsm ln whlch Lhere ls an exLracellular deposlLlon of

paLhologlcal lnsoluble flbrlllar proLelns ln organs and Llssues CharacLerlsLlcally Lhe amylold proLeln
conslsLs of pleaLed sheeLs LhaL are responslble for lLs lnsolublllLy and reslsLance Lo proLeolysls
Amyloldosls can be acqulred or lnherlLed ClasslflcaLlon ls based on Lhe naLure of Lhe precursor
plasma proLelns LhaL form Lhe flbrlllar deposlLs 1he process for Lhe producLlon of Lhese flbrlls
appears Lo be mulLlfacLorlal and dlffers amongsL Lhe varlous Lypes of amylold
1 4L omy/oidosis {immunoq/obu/in /iqht choinossocioted)
1hls ls a plasma cell dyscrasla relaLed Lo mulLlple myeloma ln whlch clonal plasma cells ln Lhe bone
marrow produce lmmunoglobullns LhaL are amyloldogenlc 1hls may be Lhe ouLcome of
desLablllzaLlon of llghL chalns owlng Lo subsLlLuLlon of parLlcular amlno aclds lnLo Lhe llghL chaln
varlable reglon 1here ls a clonal domlnance of amylold llghL (AL) chalns elLher Lhe domlnanL or
lsoLype whlch are excreLed ln Lhe urlne (8ence !ones proLelns) 1hls Lype of amylold ls ofLen
assoclaLed wlLh lymphoprollferaLlve dlsorders such as myeloma WaldensLrms
macroglobullnaemla or nonPodgklns lymphoma lL rarely occurs before Lhe age of 40 years
1he cllnlcal feaLures are relaLed Lo Lhe organs lnvolved 1hese lnclude Lhe kldneys (presenLlng wlLh
proLelnurla and Lhe nephroLlc syndrome) and Lhe hearL (presenLlng wlLh hearL fallure) AuLonomlc
and sensory neuropaLhles are relaLlvely common and carpal Lunnel syndrome wlLh weakness and
paraesLhesla of Lhe hands may be an early feaLure Sensory neuropaLhy ls common 1here ls an
absence of cenLral nervous sysLem lnvolvemenL
Cn examlnaLlon hepaLomegaly cardlomyopaLhy polyneuropaLhy and brulslng may be seen
Macroglossla occurs ln abouL 10 of cases and perlorblLal purpura ln 13
omi/io/ omy/oidoses {tronsthyretinossocioted {411k))
1hese are auLosomally domlnanL LransmlLLed dlseases where Lhe muLanL proLeln forms amylold
flbrlls sLarLlng usually ln mlddle age 1he mosL common form ls due Lo a muLanL LransLhyreLln
whlch ls a LeLramerlc proLeln wlLh four ldenLlcal subunlLs lL ls a LransporL proLeln for Lhyroxlne and
reLlnolblndlng proLeln and malnly synLheslzed ln Lhe llver Cver 80 amlno acld subsLlLuLlons have
been descrlbed for example a common subsLlLuLlon ls LhaL of meLhlonlne for vallne aL poslLlon 30
(MeL 30) ln all raclal groups and alanlne for Lhreonlne (Ala 60) ln Lhe Lngllsh and lrlsh 1hese
subsLlLuLlons desLablllze Lhe proLeln whlch preclplLaLes followlng sLlmulaLlon and can cause
dlsorders such as famlllal amyloldoLlc polyneuropaLhy (lA) cardlomyopaLhy or Lhe nephroLlc
syndrome Ma[or focl of lA occur ln orLugal !apan and Sweden
Cllnlcally perlpheral sensorlmoLor and auLonomlc neuropaLhy are common wlLh sympLoms of
auLonomlc dysfuncLlon dlarrhoea and welghL loss 8enal dlsease ls less prevalenL Lhan wlLh AL
amyloldosls Macroglossla does noL occur Cardlac problems are usually Lhose of conducLlon 1here
may be a famlly hlsLory of unldenLlfled neurologlcal dlsease
CLher heredlLary sysLemlc amyloldoses lnclude oLher famlllal amylold polyneuropaLhles (eg
orLuguese lcelandlc uuLch) 1here ls a famlllal CreuLzfeldL!akob dlsease ln famlllal MedlLerranean
fever renal amyloldosls ls a common serlous compllcaLlon

keoctive systemic {secondory 44) omy/oidoses
1hese are due Lo amylold formed from serum amylold A (SAA) whlch ls an acuLe phase proLeln lL ls
Lherefore relaLed Lo chronlc lnflammaLory dlsorders and chronlc lnfecLlon
Cllnlcal feaLures depend on Lhe naLure of Lhe underlylng dlsorder Chronlc lnflammaLory dlsorders
lnclude rheumaLold arLhrlLls lnflammaLory bowel dlsease and unLreaLed famlllal MedlLerranean
fever ln developlng counLrles lL ls sLlll assoclaLed wlLh lnfecLlous dlseases such as Luberculosls
bronchlecLasls and osLeomyellLls AA amyloldosls ofLen presenLs wlLh chronlc kldney dlsease wlLh
hepaLomegaly and splenomegaly Macroglossla ls noL a feaLure and cardlac lnvolvemenL ls rare 1he
degree of renal fallure correlaLes wlLh Lhe SAA level ln a more favourable ouLcome ln paLlenLs wlLh
low normal levels
ther omy/oides
i erebro/ omy/oidosis 4/theimers diseose ond tronsmissib/e sponqiform
encepho/opothy
1he braln ls a common slLe of amylold deposlLlon alLhough lL ls noL dlrecLly affecLed ln any form of
acqulred sysLemlc amyloldosls lnLracerebral and cerebrovascular amylold deposlLs are seen ln
Alzhelmers dlsease MosL cases are sporadlc buL heredlLary forms caused by muLaLlons have been
reporLed ln heredlLary sponglform encephalopaLhles several amylold plaques have been seen
Amylold deposlLs are frequenLly found ln Lhe elderly parLlcularly cerebral deposlLs of A4 proLeln
1hls ls also seen ln uowns syndrome ApoproLeln L lnLeracLs dlrecLly wlLh A4 proLeln ln senlle
plaques and neuroflbrlllary Langles ln Lhe braln 1he gene for apoproLeln L ls on chromosome 19 and
may be a suscepLlblllLy facLor ln Lhe aeLlology of Alzhelmers dlsease
ii Loco/ omy/oidosis
ueposlLs of amylold flbrlls of varlous Lypes can be locallzed Lo varlous organs or Llssues (eg skln
hearL and braln)
iii io/ysisre/oted omy/oidosis
1hls ls due Lo Lhe
2
mlcroglobulln produclng amylold flbrlls ln chronlc dlalysls paLlenLs lL frequenLly
presenLs wlLh Lhe carpal Lunnel syndrome
D|agnos|s
1hls ls based on cllnlcal susplclon and lf posslble on Llssue hlsLology Amylold ln Llssues appears as
an amorphous homogeneous subsLance LhaL sLalns plnk wlLh haemaLoxylln and eosln and sLalns red
wlLh Congo red lL also has a green fluorescence ln polarlzed llghL 1lssue can be obLalned from Lhe
recLum gums or abdomlnal faL 1he bone marrow may show plasma cells ln amyloldosls or a
lymphoprollferaLlve dlsorder A paraproLelnaemla and proLelnurla wlLh llghL chalns ln Lhe urlne may
also be seen ln AL amyloldosls ln secondary or reacLlve amyloldosls Lhere wlll be an underlylng
dlsorder SclnLlgraphy uslng
123
llabelled serum amylold componenL ls useful for Lhe assessmenL of
AL A118 and AA amyloldosls buL lL ls noL wldely avallable and ls expenslve
1reatment
1hls ls sympLomaLlc or Lhe LreaLmenL of Lhe assoclaLed dlsorder 1he nephroLlc syndrome and
congesLlve cardlac fallure requlre Lhe relevanL Lheraples 1reaLmenL of any lnflammaLory source or
lnfecLlon should be lnsLlLuLed Colchlclne may help famlllal MedlLerranean fever LprodlsaLe whlch
lnLerferes wlLh lnLeracLlons beLween amylold proLelns and glycosamlnoglycans lnhlblLs
polymerlzaLlon of amylold flbrlds lL slows Lhe fall ln renal funcLlon ln AA amyloldosls ChemoLherapy
wlLh nephalan plus dexameLhasone ls showlng some efflcacy ln AL amyloldosls ln A118 amyloldosls
where LransLhyreLln ls predomlnanLly synLheslzed ln Lhe llver llver LransplanLaLlon (when Lhere
would be a dlsappearance of Lhe muLanL proLeln from Lhe blood) ls consldered as Lhe deflnlLlve
Lherapy