Wild-type transthyretin amyloid

Wild-type Transthyretin Amyloidosis

Structure of transthyretin protein. Image courtesy of Wikimedia Commons.

Wild-type transthyretin amyloidosis (ATTRwt), also known as senile systemic amyloidosis, is a rare, late-onset, progressive, and fatal disease characterized by the deposition of wild-type transthyretin (TTR) protein in various organs and tissues.

Etiology

ATTRwt is caused by the misfolding and aggregation of the transthyretin protein, which is primarily produced in the liver. The exact mechanism of TTR misfolding and aggregation is not fully understood, but it is believed to involve a multi-step process that includes tetramer dissociation, monomer misfolding, and aggregation into amyloid fibrils.

Clinical Presentation

Patients with ATTRwt typically present in their seventh decade of life with progressive cardiac symptoms, including heart failure, arrhythmias, and conduction system disease. Non-cardiac manifestations can also occur, such as carpal tunnel syndrome, lumbar spinal stenosis, and gastrointestinal symptoms.

Diagnosis

Diagnosis of ATTRwt is often challenging due to its non-specific symptoms and the need for specialized diagnostic tests. It typically involves a combination of clinical assessment, imaging studies, and laboratory tests, including biopsy of affected tissues and genetic testing.

Treatment

Treatment of ATTRwt is primarily supportive and aimed at managing symptoms. Therapies that target the underlying disease process, such as tafamidis, are currently under investigation.

Prognosis

The prognosis of ATTRwt is generally poor, with a median survival of 3-5 years from the onset of heart failure symptoms. Early diagnosis and treatment can potentially improve the prognosis.

See Also

• Amyloidosis
• Transthyretin-related hereditary amyloidosis
• Familial amyloid cardiomyopathy