Sorted By Test Name - Mayo Medical Laboratories

TTRX
83674
Clinical Information: The systemic amyloidoses are a number of disorders of varying etiology
characterized by extracellular protein deposition. The most common form is an acquired amyloidosis
secondary to multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) in which
the amyloid is composed of immunoglobulin light chains. In addition to light chain amyloidosis, there are
a number of acquired amyloidoses caused by the misfolding and precipitation of a wide variety of
proteins. There are also hereditary forms of amyloidosis. Due to the clinical overlap between the acquired
and hereditary forms, it is imperative to determine the specific type of amyloidosis in order to provide an
accurate prognosis and consider appropriate therapeutic interventions. The most common hereditary
amyloidosis is familial transthyretin amyloidosis; an autosomal dominant disorder caused by mutations in
the transthyretin (TTR) gene. The resulting amino acid substitutions lead to a relatively unstable,
amyloidogenic TTR protein. Most individuals begin to exhibit clinical symptoms between the third and
seventh decades of life. Typically, TTR-associated amyloidosis is progressive over a course of 5 to 15
years and the most common cause of death is cardiomyopathy. Affected individuals may present with a
variety of symptoms, including peripheral neuropathy, blindness, cardiomyopathy, nephropathy,
autonomic nervous dysfunction, or bowel dysfunction. More than 90 mutations have now been identified
within the TTR gene which cause TTR-associated familial amyloidosis. Most of the mutations described
to date are single base pair changes that result in an amino acid substitution. Some of these mutations
correlate with the clinical presentation of amyloidosis. However, several different mutations have been
identified which exhibit considerable clinical overlap. It is important to note that this assay does not detect
mutations associated with non-TTR forms of familial amyloidosis. Therefore, it is important to first test
an affected family member to determine if TTR is involved and to document a specific mutation in the
family before testing at risk individuals.
Useful For: Testing of at-risk individuals when a mutation has been identified in an affected family
member
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Benson MD: The hereditary amyloidoses. Best Pract Res Clin Rhematol
2003;17:909-27 2. Eneqvist T, Sauer-Eriksson AE: Structural distribution of mutations associated with
familial amyloidotic polyneuropathy in human transthyretin. Amyloid 2001;8:149-168 3. Connors LH,
Lim A, Prokaeva VA, et al: Tabulation of human transthyretin (TTR) variants, 2003. Amyloid
2003;10:160-184
Amyloidosis, Transthyretin-Associated Familial, Reflex, Blood
Clinical Information: The systemic amyloidoses are a group of diseases that result from the
abnormal deposition of amyloid in various tissues of the body. They have been classified into 3 major
types: primary, secondary, and hereditary. The most common form of amyloidosis (AL) is a disease of the
bone marrow called primary systemic AL (immunoglobulin light chain or AL). Secondary AL usually
occurs in tandem with chronic infectious or inflammatory diseases, such as rheumatoid arthritis,
tuberculosis, or osteomyelitis. Hereditary AL is the least common form. Determining the specific type of
AL is imperative in order to provide both an accurate prognosis and appropriate therapies. Familial or
hereditary transthyretin AL is an autosomal dominant disorder caused by mutations in the transthyretin
gene (TTR). The resulting amino acid substitutions lead to a relatively unstable, amyloidogenic
transthyretin (TTR) protein. Most individuals begin to exhibit clinical symptoms between the third and
seventh decades of life. TTR-associated AL is progressive over a course of 5 to 15 years and usually ends
in death from cardiac or renal failure, or malnutrition. Affected individuals may present with a variety of
symptoms including peripheral neuropathy, blindness, cardiomyopathy, nephropathy, autonomic nervous
dysfunction, or bowel dysfunction. More than 90 mutations have now been identified within the TTR
gene, which cause TTR-associated familial AL. Most of the mutations described to date are single base
pair changes that result in an amino acid substitution. Some of these mutations correlate with the clinical
presentation of AL. The Division of Laboratory Genetics recommends a testing strategy that includes both
protein analysis by mass spectrometry (MS) and TTR gene analysis by DNA sequencing (AMYL/83667
Amyloidosis, Transthyretin-Associated Familial, DNA Sequence, Blood) for patients where
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