Preferred Label : Amyloidosis, hereditary systemic 1;
Symbol : AMYLD1;
CISMeF acronym : FAP;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : Hereditary amyloidosis, transthyretin-related; Transthyretin amyloidosis; Amyloid polyneuropathy, familial; FAP;
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.;
Inheritance : Autosomal dominant;
Molecular basis : Caused by mutation in the transthyretin gene (TTR, 176300.0001);
Prefixed ID : #105210;
Origin ID : 105210;
UMLS CUI : C2751492;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- DO Cross reference
- False automatic mappings
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- See also inter- (CISMeF)
- Semantic type(s)
- UMLS correspondences (same concept)
- Validated automatic mappings to BTNT
- Validated automatic mappings to NTBT
