Transthyretin amyloidosis: an over review

Amyloidosis refers to the extracellular deposition of fibrils that are composed 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. The main neuropathic feature of transthyretin amyiloidosis is a progressive sensorimotor and autonomic neuropathy. 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 demonstrated 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. For patients with transthyretin-primary familial amyloidosis who have mild or moderate disease and a diagnosis confirmed by genetic testing and biopsy, liver transplant is the current standard of care.