| Popis: |
Background: Amyloidosis is a multisystem disorder characterised by abnormal protein folding, in which proteins adopt an abnormal conformation and deposit as insoluble fibrils that disrupt tissue structure and function. Aims and Methods: To characterise the phenotype of the heredo-familial forms of systemic amyloidosis, the role of solid organ transplantation in the different systemic amyloidosis syndromes and to evaluate the gastroenterological and hepatological causes and sequaelae of systemic amyloidosis. These features were sought in patients followed at the UK National Amyloidosis Centre between 1984 and 2011. Results and Conclusions: Familial amyloid polyneuropathy associated with the T60A transthyretin variant has a prominent cardiac phenotype, which negatively impacts upon prognosis. Furthermore this cardiac phenotype has a negative impact upon survival in those who undergo liver transplantation to eliminate variant transthyretin, which is synthesised in the liver, not only by increasing operative risk but also as there is likely ongoing cardiac amyloid deposition associated with wild-type transthyretin from the liver graft. In the face of failing organ function, liver and renal transplantation in hereditary lysozyme amyloidosis (ALys) appears feasible, despite ongoing amyloidogenesis and the risk of recurrent graft amyloid, due to slow turnover of amyloid. Similarly, renal and cardiac transplantation in AL amyloidosis and renal transplantation in AA amyloidosis appear favourable when strategies to suppress amyloidogenic precursor protein production are employed in tandem. Gastrointestinal and hepatic amyloid are recognised in systemic amyloidosis. In ALys both are prevalent; the former is associated with endoscopic abnormalities and the latter may be asymptomatic or present as hepatic rupture. In patients diagnosed with amyloid by liver biopsy after presenting with deranged liver biochemistry, AL amyloidosis is the commonest cause and although this presentation has been historically associated with a poor prognosis as there is frequently concomitant extra-hepatic amyloid, in those who achieve a good clonal response to chemotherapeutic regimes in the modern era of treatment a survival advantage is conferred. Primary gastrointestinal disease, such as inflammatory bowel disease, can cause systemic AA amyloidosis. Tight inflammatory control, guided by serial serum amyloid A protein levels, benefits amyloidotic kidneys, as does aggressive treatment of physiological renal stresses, such as sepsis. Systemic AL amyloidosis is commonly associated with malnutrition, especially when there is multisystem amyloid. Malnutrition in this group is associated with a poor quality of life and worse survival and it would appear therefore to be a potential target for intervention studies. |
