The familial amyloid neuropathies (or familial amyloidotic neuropathies, neuropathic heredofamilial amyloidosis, familial amyloid polyneuropathy) are a rare group of autosomal dominant diseases wherein the autonomic nervous system and/or other

nerves A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called ...

are compromised by protein aggregation and/or amyloid fibril formation.

Classification

The aggregation of one precursor protein leads to

peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

and/or autonomic nervous system dysfunction. These proteins include:

transthyretin Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol' ...

(ATTR, the most commonly implicated protein),

apolipoprotein A1 Apolipoprotein AI (Apo-AI) is a protein that in humans is encoded by the ''APOA1'' gene. As the major component of high-density lipoprotein (HDL) particles, it has a specific role in lipid metabolism. Structure ''APOA1'' is located on chromo ...

, and

gelsolin Gelsolin is an actin-binding protein that is a key regulator of actin filament assembly and disassembly. Gelsolin is one of the most potent members of the actin-severing gelsolin/villin superfamily, as it severs with nearly 100% efficiency. Cellu ...

. Due to the rareness of the other types of familial neuropathies, transthyretin amyloidogenesis-associated polyneuropathy should probably be considered first. "FAP-I" and "FAP-II" are associated with

. ( Senile systemic amyloidosis bbreviated "SSA"is also associated with transthyretin aggregation.) "FAP-III" is also known as "Iowa-type", and involves

. "FAP-IV" is also known as " Finnish-type", and involves

Fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

, and

lysozyme Lysozyme (, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside hydrolase ...

are associated with a closely related condition, familial visceral amyloidosis. Diagnosis is confirmed by blood tests, organ biopsies, and tissue biopsies.

Genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

can also be used to confirm a mutation in the TTR gene. Although some people with a hATTR gene mutation may not experience symptoms.

Treatment

Liver transplantation Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...

has proven to be effective for ATTR familial amyloidosis due to Val30Met mutation. In 2011 the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

approved

tafamidis Tafamidis, sold under the brand names Vyndaqel and Vyndamax, is a medication used to delay disease progression in adults with certain forms of transthyretin amyloidosis. It can be used to treat both hereditary forms, familial amyloid cardiomyo ...

for this condition. The FDA rejected the application for marketing approval in the US in 2012 on the basis that the clinical trial data did not show efficacy based on a functional endpoint, and the FDA requested further clinical trials.

References

External links

{{Medical resources , DiseasesDB = , ICD10 = {{ICD10, E, 85, 1, e, 70 , ICD9 = {{ICD9, 277.3 , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = D028227 Amyloidosis Neurological disorders