Hereditary and acquired amyloid neuropathies.

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• Amyloid neuropathies encompass hereditary (FAP) and acquired forms, typically presenting as severe, progressive polyneuropathy with a poor prognosis.
• Transthyretin familial amyloid polyneuropathy (TTR-FAP) is often linked to endoneurial deposits of variant transthyretin (TTR) due to TTR gene point mutations, with Portugal being a primary endemic area.
• Acquired amyloid neuropathy primarily involves immunoglobulin light chain amyloidosis (AL), frequently associated with renal issues and monoclonal proteins.

Purpose of the Study:

• To review the diagnosis, genetic basis, and management of various amyloid neuropathies.
• To highlight the role of genetic studies in identifying FAP causes and enabling genetic counseling.
• To differentiate between hereditary and acquired amyloidosis and their respective treatments.

Main Methods:

• Review of literature on amyloid neuropathies, focusing on genetic and clinical aspects.
• Analysis of TTR gene mutations and their association with TTR-FAP.
• Comparison of diagnostic approaches and treatment strategies for different amyloidosis types.

Main Results:

• TTR-FAP is primarily caused by specific TTR gene mutations, with over 50 reported worldwide.
• Genetic testing is crucial for diagnosing FAP, identifying sporadic cases, and providing genetic counseling, including prenatal diagnosis.
• Gel-solin-FAP is a distinct, benign variant affecting Finnish patients, while AL amyloidosis involves immunoglobulin light chains and often renal complications.

Conclusions:

• Genetic analysis is fundamental for accurate diagnosis and management of amyloid neuropathies.
• Treatment strategies for amyloid polyneuropathy are diverse, ranging from liver transplantation for TTR-FAP to chemotherapy for AL amyloidosis.