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Familial Amyloid Polyneuropathy
Transthyretin (TTR) amyloidosis is an autosomal dominant disorder caused by the deposition of insoluble amyloid fibrils around peripheral nerves and in various tissues, including the heart muscle. Based on the predominant organ involvement, several distinct subtypes have been reported. Familial amyloid polyneuropathy (FAP) aka TTR amyloid neuropathy is characterized by slowly progressive, peripheral sensorimotor polyneuropathy [...]+ Mutation-specific testing + Prenatal testing
Transthyretin (TTR) amyloidosis is an autosomal dominant disorder caused by the deposition of insoluble amyloid fibrils around peripheral nerves and in various tissues, including the heart muscle. Based on the predominant organ involvement, several distinct subtypes have been reported.
Familial amyloid polyneuropathy (FAP) aka TTR amyloid neuropathy is characterized by slowly progressive, peripheral sensorimotor polyneuropathy and autonomic dysfunction. Disease onset is usually in the third to fourth decade of life. Sensory neuropathy starts in the lower extremities with paresthesia, impaired pain and temperature sensation, followed by loss of motor function. Autonomic neuropathy usually manifests with orthostatic hypotension, constipation alternating with diarrhea, vomiting, impotence or hypohidrosis. Unrelated to neuropathy, other organs manifestations may include cardiomyopathy, vitreous opacities and CNS amyloidosis.
Leptomeningeal amyloidosis aka oculoleptomeningeal amyloidosis affects predominantly the central nervous
system, sometimes combined with visual impairment.
Cardiac amyloidosis usually manifests in the sixth decade of life with progressive left ventricular hypertrophy and restrictive cardiomyopathy. In a subset of families with cardiac amyloidosis, peripheral neuropathy may be completely absent or very mild.
Treatment: Currently, the only effective treatment for FAP is an orthotopic liver transplant to stop production of misfolded amyloid protein. In patients with severe amyloid cardiomyopathy, a heart transplant may be
necessary. Different drugs designed to prevent or alleviate accumulation of TTR amyloid protein (transthyretin amyloidois inhibitors) are currently under investigation.
TTR Gene Sequencing
FORMS AND DOCUMENTS
- Clinical Utility:
- Confirmation of a clinical diagnosis
- Differentiation between cardiac amyloidosis and other cardiomypopathies
- Carrier testing in at-risk family members
- Prenatal diagnosis
- Lab Method:
- Capillary Sequencing
- Test Code:
- Turnaround Time:
- 4-5 weeks
- Preferred Specimen:
- 2-5 mL Blood - Lavender Top Tube
- CPT Codes:
- Billing Information:
- View Cardiology Billing Policy
- ICD Codes:
- 425.7: Nutritional and metabolic cardiomyopathy; Code first underlying disease, as: amyloidosis (277.30-277.39), beriberi (265.0), cardiac glycogenosis (271.0), mucopolysaccharidosis (277.5), thyrotoxicosis (242.0-242.9)
- 277.39: Other amyloidosis, Hereditary cardiac amyloidosi,s Inherited systemic amyloidosis, Neuropathic (Portuguese) (Swiss) amyloidosis, Secondary amyloidosis
- 277.3: Amyloidosis, unspecified Amyloidosis NOS
- Seikijima Y et al. Transthyretin amyloidosis, In: GeneReviews. Last Update: March 15, 2006. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tfap
- Hou et al. (2007) Transthyretin and familial amyloidotic polyneuropathy FEBS 274, 1637-50
- Jacobson DR et al. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in Black Americans. New Eng. J. Med. 336: 466-473, 1997
- Coelho T et al. A study of 159 Portuguese patients with familial amyloidotic polyneuropathy (FAP) whose parents were both unaffected. J. Med. Genet. 31: 293-299, 1994
- Holmgren G et al. Geographical distribution of TTR met-30 carriers in northern Sweden: discrepancy between carrier frequency and prevalence rate. J. Med. Genet. 31: 351-354, 1994
- Ikeda S et al. Asymptomatic homozygous gene carrier in a family with type I familial amyloid polyneuropathy. Europ. Neurol. 32: 308-313, 1992
- Holmgren G et al. Homozygosity for the transthyretin-met30-gene in seven individuals with familial amyloidosis with polyneuropathy detected by restriction enzyme analysis of amplified genomic DNA sequences. Clin. Genet. 41: 39-41, 1992
- Online Mendelian Inheritance in Man. www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM
- Ando, Y. et al. (2005) Transthyretin-related Familial Amyloidotic Polyneuropathy Arch Neurol 62, 1057-62
- Saraiva, M.J.M. (2001) Transthyretin Mutations in Hyperthyroxinemia and Amyloid Disease Hum Mutat 17, 493-503
- Sekijima et al. (2005) The biological and chemical basis for tissue-selective amyloid disease Cell 121, 73-85