Amyloidosis

Amyloidosis is an umbrella term for a group of diseases characterized by deposits of abnormally altered, insoluble proteins (amyloid) in intra- and extracellular spaces. In familial amyloidosis, which is inherited in an autosomal-dominant manner, these abnormal proteins arise due to genetic mutations. One of the most commonly affected proteins is the blood protein transthyretin (TTR), produced almost exclusively in the liver, giving rise to transthyretin amyloidosis (ATTR). With a prevalence of approximately 1.1 per 100,000, ATTR typically presents in adulthood and offers only limited treatment options. Insoluble transthyretin deposits primarily in the peripheral nervous system or the myocardium, causing tissue damage. Depending on the organs involved, two classic forms are distinguished:

• Transthyretin-associated familial amyloid polyneuropathy
• Transthyretin-associated familial amyloid cardiomyopathy

However, in about 80% of cases a mixed presentation occurs, with patients experiencing both neurological and cardiac symptoms (neuropathy and cardiomyopathy). Early manifestations of ATTR are often non-specific. Typically, patients first develop loss of sensory function in the hands and feet (impaired temperature perception, altered pain sensation), which progresses over time and is accompanied by declining motor abilities. Patients frequently suffer from neuropathic pain and autonomic dysfunction, often associated with significant weight loss. Depending on the mutation, the gastrointestinal tract, eyes, and kidneys may also be involved. Cardiac involvement typically includes diastolic dysfunction, arrhythmias, and heart failure.

Studies indicate that neurological impairments are associated with loss of muscle strength and coordination. Walking becomes increasingly difficult, and the risk of falls rises. Overall reductions in physical capacity and increasing immobility lead to a significant decline in quality of life for people with ATTR.

Targeted exercise therapy may help reduce the accompanying symptoms of ATTR and sustainably improve quality of life. Early studies report beneficial effects of structured training on body composition and physical performance in various amyloidosis subgroups.