The reference OMIM entry for this protein is 105210

Amyloidosis, hereditary, transthyretin-related
Hereditary amyloidosis, transthyretin-related
Transthyretin amyloidosis
Amyloid polyneuropathy, familial; fap amyloidosis, leptomeningeal, transthyretin-related, included
Amyloid cardiomyopathy,

A number sign (#) is used with this entry because this form of hereditary amyloidosis is caused by mutations in the TTR gene (176300) on chromosome 18q11-q12, encoding transthyretin.

DESCRIPTION

Hereditary amyloidoses are a clinically and genetically heterogeneous group of autosomal dominantly inherited diseases characterized by the deposit of unsoluble protein fibrils in the extracellular matrix (summary by Hund et al., 2001). Patients with transthyretin amyloidosis typically present with polyneuropathy, carpal tunnel syndrome, autonomic insufficiency, cardiomyopathy, and gastrointestinal features, occasionally accompanied by vitreous opacities and renal insufficiency. In later stages of the disease severe diarrhea with malabsorption, cachexia, incapacitating neuropathy, severe cardiac disturbances, and marked orthostatic hypotension dominate the clinical picture. Death usually occurs 5 to 15 years after onset of symptoms. Before the emergence of molecular genetics, hereditary amyloidoses were classified into 4 subtypes according to symptom constellation and ethnic origin (summary by Hund et al., 2001). The course of disease beginning with sensorimotor polyneuropathy that starts in early adulthood symmetrically at the legs and progresses rather rapidly to incapacitate the patient within a few years has been labeled familial amyloid polyneuropathy type I (FAP I), also known as Portuguese, Portuguese-Swedish-Japanese, or Andrade type. FAP I can be considered the prototype of the manifestation of hereditary TTR amyloidosis. The overwhelming majority of cases of FAP I result from a val30-to-met (V30M; 176300.0001) substitution. A course of disease with neuropathy beginning at the hands and frequent carpal tunnel operations has been designated FAP II, also known as the Indiana/Swiss (176300.0006) or Maryland/German (176300.0003) type. Vitreous opacities occur early in the disease course, whereas impotence and renal insufficiency are rare. Amyloidosis due to mutations in the APOA1 gene (107650) has been referred to as FAP III or Iowa type (see 105200 and 107680.0010). The Finnish type of amyloidosis (105120) has been referred to as FAP IV and is caused by mutations in gelsolin (137350). Systems based on clinical phenotypes have historically been used to classify the amyloidoses, but emphasis on the characterization of the amyloid fibril protein has proved more useful (Saraiva, 2002). In addition to hereditary amyloidosis, 2 other major forms of systemic amyloidosis exist. Immunoglobulin (AL) amyloidosis, formerly known as primary amyloidosis, is caused by the accumulation of monoclonal immunoglobulin (Ig) light chains as amyloid fibrils. Reactive (AA) amyloidosis, formerly known as secondary amyloidosis, is associated with chronic inflammatory diseases (e.g., rheumatoid arthritis, 180300; familial Mediterranean fever, 249100), and fibrils are derived from the circulating acute-phase reactant serum amyloid A protein (see 104750). Ando et al. (2005) provided a review of transthyretin-related familial amyloid polyneuropathy. The authors stated that the phenotypes can be classified into neuropathic, oculoleptomeningeal, and cardiac.

CLINICAL FEATURES

- Familial Amyloid Polyneuropathy Familial amyloid polyneuropathy (FAP) was described by Andrade (1952) in the northern area of Portugal (reviewed by Saraiva, 2001). Kindreds had an age of onset of clinical symptoms in the third or fourth decade of life. Early impairment of tem ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 105210 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).