Results are reported in 10-21 days.
Transthyretin (TTR) amyloidosis is a hereditary, multisystem disease caused by abnormal formation and extracellular deposit of TTR protein fibrils in various tissues.
Inheritance is autosomal dominant, but family history may appear to be negative in the majority of patients for several reasons. Approximately 2/3 of cases arise from new mutations. Age of onset is typically in the thirties but varies by decades within and between populations. Penetrance is <100% with widely ranging estimates for the same mutation in different populations. Genotypes do not predict the onset, severity, or specific symptoms for the 100+ mutations, but many mutations tend to associate with one of three broad phenotypes of TTR amyloidosis.
The most common mutation V30M causes progressive autonomic and sensorimotor dysfunction called familial amyloid polyneuropathy. Symptoms include carpal tunnel syndrome, parasthesia followed by loss of sensation and disability in hands and feet, constipation, diarrhea, vomiting, incontinence, urinary retention, anhidrosis, and/or orthostatic hypotension. Cardiomyopathy and vitreous opacities are common in this type.
Patients with a cardiac-predominant form have restrictive cardiomyopathy and possibly conduction defects but neuropathy is absent or less evident. One mutation associated with this type, V122I, is carried by approximately 3% of African-Americans.
The leptomeningeal form generally spares sensory and autonomic functions but amyloid deposits on CNS tissues cause hydrocephalus, seizures, ataxia, dementia, psychosis, motor impairment, and/or intracranial hemorrhage.
Non-amyloid and protective TTR mutations are known. Senile systemic amyloidosis results from abnormal deposition of non-mutant TTR protein.
The Ambry Test is full gene sequence analyses of the TTR gene. Results are reported 10-21 days after testing is initiated.
Other diagnostic tests for TTR Amyloidosis include histo- and immunocytochemical analysis of biopsy tissue and analysis of serum or cerebrospinal fluid for abnormal TTR protein. Molecular testing provides a less invasive option with higher sensitivity and specificity.
General Test Information
The Ambry Test: Transthyretin Amyloidosis
(Abobe PDF document)
The following CPT Codes for the Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:
Ambry Test: TTR Amyloidosis
83891, 83894, 83898, 83904, 83909, 83912
CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.
Disclaimer:
This test was developed and its performance characteristics were determined by Ambry
Genetics Corporation. The laboratory is regulated under the Clinical Laboratory
Improvement Amendments 2003 as qualified to perform nonwaived testing. The Ambry
Test: TTR Amyloidosis analyzes the following types of mutations: nucleotide substitutions,
small deletions, small insertions, and small indels. It is not intended to analyze
the following types of mutations: gross insertions, gross rearrangements, deep intronic
variations, and other unknown abnormalities. The pattern of mutation types varies
with the gene tested and the Ambry Test detects a high but variable percentage of
known and unknown mutants of the classes stated. A negative result from the analysis
cannot rule out the possibility that the tested individual carries a rare unexamined
mutation or mutation in the undetectable group. The Ambry Test: TTR Amyloidosis
is designed and validated to be capable of detecting about 99% of TTR mutations
(considering less than 1% to be the other types of mutations). Amyloidosis is a
complex clinical disorder, which in some cases is due to alterations in the TTR
gene generally detected by the Ambry Test: TTR Amyloidosis except as noted above.
Mutations in other genes or the regions not tested by the Ambry Test: TTR Amyloidosis
can also give rise to clinical conditions similar to TTR amyloidosis. Although molecular
tests are highly accurate, rare diagnostic errors may occur. Possible diagnostic
errors include sample mix-up, erroneous paternity identification, technical errors,
and genotyping errors. Genotyping errors can result from trace contamination of
PCR reactions, from maternal cell contamination in fetal samples, from rare genetic
variants, which interfere with analysis, or from other sources. This report does
not represent medical advice. Any questions, suggestions, or concerns regarding
interpretation of results should be forwarded to a genetic counselor, medical geneticist,
or physician skilled in interpretation of the relevant medical literature. References
are available upon request.
