Transthyretin amyloidosis: an over review

Abstract

Amyloidosis is the extracellular deposition of fibrils, these consist of low molecular weight subunits of a variety of serum proteins. The most common familial amyloidosis is caused by the transthyretin protein. People who are born with inherited mutations in the transthyretin gene produce abnormal, ("variant") transthyretin throughout their liver. The clinical manifestations vary, depending upon the particular substitution, but result either in neuropathy, cardiomyopathy, or both. One of the most common hereditary transthyretin amyloid cardiomyopathies is caused by the Val122IIe mutation. Progressive amyloid deposition in the myocardium and/or in the electrical conduction system is responsible for restrictive cardiomyopathy and unpredictable episodes of arrhythmias and/or severe conduction disorders. The vast majority of transthyretin-familial amyloidotic polyneuropathy cases are associated with Val30Met mutation. Progressive sensorimotor and autonomic neuropathy is the main neuropathic feature of transthyretin amyiloidosis. The first step in evaluating a patient with transthyretin amyloidosis consists in establishing the diagnosis and then evaluating the extent of disease. Deposition of amyloid via tissue can be established by Congo red staining of biopsy specimens. In all cases, amyloid typing has to be completed by transthyretin gene sequencing and by immunofixation electrophoresis of serum and urine. Current treatment options for patients with transthyretin amyiloidosis are limited. Patients with transthyretin-primary familial amyloidosis with mild or moderate disease, a diagnosis confirmed by genetic testing and biopsy, liver transplant is the current treatment standard.