Transthyretin amyloidosis, the most common form of familial amyloidosis, is a systemic disorder characterized by the extracellular deposition of amyloid fibrils causing organ dysfunction and failure.
| Clinical Features | Transthyretin (TTR) amyloidosis can present as infiltrative cardiomyopathy (familial amyloid cardiomyopathy, FAC), progressive, axonal sensory autonomic and motor neuropathy (familial amyloidotic polyneuropathy, TTR-FAP), central nervous system amyloidosis (CNSA), and senile systemic amyloidosis (SSA). |
| Incidence | Rare |
| Gene | TTR |
| Inheritance | Autosomal dominant |
| Penetrance | Incomplete with variable expression |
| Disease Pathogenesis | Transthyretin (TTR) is a thyroxine and Vitamin A plasma transport protein. Mutations in the protein destabilize it causing it to misfold and aggregate into amyloid fibrils that accumulate in various organs and tissues. While FAC, FAP and CNSA are caused due to mutations in TTR, SSA results form the deposition of wild type-TTR in men after the age of 60 years. |
| Indications for Molecular Testing | Confirm or establish diagnosis Predictive testing Prenatal diagnosis |
| Test Information | TTR Gene exons and intron/exon boundaries are analyzed subsequent to Sanger sequencing. Mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations. Exonic or whole-gene deletions/duplications will not be detected. Additionally, a negative result does not rule out causal gene mutations as the promoter region and cryptic splicing mutations are not investigated. |
| Clinical Sensitivity | >99% |
| Turnaround Time | 2-4 weeks |
Sample and Shipping Information
| Specimen | Whole blood drawn in lavender top (EDTA) tube in a volume of 3-5cc (Adults/Children) and 3 cc (infant) |
| Shipping | Refrigerate sample until time of shipping. Ship sample at room temperature in an insulated container by overnight delivery. |
| Causes for Rejection | Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container. |
References
Ando Y, Coelho T, Berk JL, Cruz MW, Ericzon BG, Ikeda S, Lewis WD, Obici L, Planté-Bordeneuve V, Rapezzi C, Said G, Salvi F. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013 Feb 20;8:31.
Coelho T, Maurer MS, Suhr OB. THAOS – The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013 Jan;29(1):63-76.
Sekijima Y, Wiseman RL, Matteson J, Hammarstrom P, Miller SR, Sawkar AR, Balch WE, Kelly JW. The biological and chemical basis for tissue-selective amyloid disease. Cell. 2005;121:73–85.
Resources
Amyloidosis Foundation (AF)
7151 North Main Street
Suite 2
Clarkston MI 48346
info@amyloidosis.org
www.amyloidosisresearchfoundation.org
American Liver Foundation
75 Maiden Lane
Suite 603
New York NY 10038
Phone: 800-465-4837
Toll-Free: 212-668-1000
Fax: 212-483-8179
info@liverfoundation.org
www.liverfoundation.org
Transthyretin Amyloidosis Outcomes Survey (THAOS)
Phone: 617-252-5500
Fax: 617-252-5501
THAOS@foldrx.com
Transthyretin Amyloidosis Outcomes Survey