Type V familial amyloid polyneuropathy (FAP), also known as ATTR V30M amyloidosis, is a rare genetic disorder characterized by the abnormal accumulation of amyloid protein in multiple organs, particularly in the peripheral nerves. This condition is caused by a mutation in the transthyretin (TTR) gene, resulting in the production of a variant protein that tends to misfold and form amyloid fibrils.
FAP typically presents with a progressive peripheral neuropathy, which includes sensory, motor, and autonomic dysfunction. Patients may experience symptoms such as numbness, tingling, weakness, muscle atrophy, and difficulties with coordination and balance. Additionally, autonomic symptoms can manifest as gastrointestinal disturbances, urinary problems, cardiovascular instability, and sexual dysfunction.
Besides peripheral neuropathy, Type V FAP can involve other organs, including the heart, kidneys, and eyes. Cardiomyopathy, characterized by an enlarged heart and impaired cardiac function, is a common manifestation of the disease. Kidney involvement may lead to proteinuria and kidney dysfunction. Ocular findings can include vitreous opacities, visual impairment, and glaucoma.
Type V FAP is an autosomal dominant disorder, meaning that an affected person has a 50% chance of passing the mutation to each of their children. The age of symptom onset and disease progression can vary widely among affected individuals, even within the same family.
Currently, liver transplantation is the only curative treatment for Type V FAP. This procedure aims to remove the source of the variant transthyretin protein and slow down or halt disease progression. Other therapies such as gene silencing drugs and TTR stabilizers are being developed as potential treatments.
