Familial Portuguese Polyneurotic Amyloidosis

Definition

Familial Portuguese Polyneurotic Amyloidosis (FAP), also known as ATTR Val30Met amyloidosis, is a rare inherited disorder characterized by the abnormal accumulation of amyloid protein in various organs, predominantly affecting the peripheral nervous system.

Causes

FAP is caused by a specific mutation in the transthyretin (TTR) gene, which leads to the production of a variant TTR protein that is prone to misfolding and aggregation. This misfolded protein accumulates as amyloid in tissues and organs, disrupting their normal structure and function.

Symptoms

The symptoms of FAP primarily manifest due to the deposition of amyloid in nerve tissues. Common symptoms include peripheral neuropathy, which leads to progressive sensory loss, muscle weakness, and autonomic dysfunction. Other affected organs, such as the heart and gastrointestinal tract, may also exhibit symptoms.

Diagnosis

Diagnosis of FAP involves a combination of clinical evaluation, family history analysis, and confirmatory genetic testing to identify the specific TTR mutation. Other diagnostic tests, such as nerve biopsies, imaging studies, and laboratory analysis of amyloid deposits, may also support the diagnosis.

Treatment

Treatments for FAP focus on reducing the production of abnormal TTR protein or managing the symptoms associated with amyloid deposition. Liver transplantation, aimed at replacing the faulty TTR-producing liver with a healthy one, is considered the definitive treatment option. Other therapeutic interventions include medications to stabilize the TTR protein or alleviate symptoms.

Prognosis

Prognosis for FAP varies depending on the specific TTR mutation, symptom severity, and the organs affected. The disease generally progresses gradually, leading to a decline in quality of life. Without treatment, FAP can be life-threatening, especially when cardiac or gastrointestinal complications arise.