Andrade's disease or familial amyloid polyneuropathy
Analysis of mutations associated with Andrade disease or familial amyloid polyneuropathy (FAP).
What is Andrade's disease?
Andrade’s disease or familial amyloid polyneuropathy (FAP), also known as transthyretin amyloid polyneuropathy. It is a progressive autonomic sensory-motor neuropathy that appears in adulthood.
The first manifestations are paraesthesia, pain or trophic lesions of the feet, gastrointestinal disorders or weight loss. The most pronounced sensory loss involves pain and thermal sensation. Motor loss occurs later. Autonomic features include postural hypotension and gastrointestinal and genitourinary disorders. Cardiac involvement is common, as are ocular or renal complications.
Although clinically heterogeneous and its clinical presentation depends on genotype and geographic origin, Andrade’s disease is severe and disabling. Death occurs on average about 11 years after the onset of the first symptoms and may occur suddenly or as a result of infections or cachexia.
Analysis of Andrade's disease at Genosalut
At Genosalut we analyse the most frequent variant in the Balearic Islands (TTR Val30Met) as well as the other mutations related to this disease.
We also offer personalised advice and genetic counselling to affected families.
In the case of the Mallorcan population, first of all, the presence of the TTR Val30Met variant (NM_000371.4(TTR):c.148G>A (p.Val50Met)
TTR Val30Met, TTR V30M, rs28933979) by sequencing or real-time PCR.
Other mutations associated with Andrade disease
We also analyse the approx. 40 mutations associated with this disease by sequencing (exons 1, 2, 3 and 4) or exome analysis.
Our value proposal
How is Andrade's disease transmitted?
Andrade disease is transmitted as an autosomal dominant trait of variable penetrance and is caused by mutations in the TTR gene.
More than 40 TTR mutations have been identified so far, associated with varying patterns of organ involvement, age of onset and disease progression.
The most common variant is the TTR Val30Met substitution (rs28933979), for which several endemic foci have been identified, especially in Portugal, Japan and Sweden. In Spain there are endemic foci in Mallorca and Huelva. The TTR Val30Met phenotype varies between these countries. Protective factors are thought to be involved. In the case of the Mallorcan population, the TTR Gly6Ser polymorphism (rs28933979) could be one of these protective factors. The worldwide prevalence is unknown, although the prevalence among the general population in Japan has recently been estimated at 1:1000000.
Prevention and peace of mind with the genetic tests of Genosalut
How can I request a genetic test for Andrade's disease?
Frequently asked questions
What tests are necessary for the diagnosis of Andrade's disease?
Detection of amyloid-associated TTR mutations is required for diagnosis. Even so, the identification of a disease-causing mutation is not considered diagnostic, because genetic penetrance is variable. Clinical observation and biopsy of tissues (such as nerve, kidney, labial salivary glands, subcutaneous fatty tissue or rectal mucosa) are necessary for a definitive diagnosis: amyloid deposits are detected by Congo red staining by conventional light microscopy and by green birefringence by polarised light microscopy.
Utility of genetic counselling for familial amyloid polyneuropathy
At Genosalut we offer genetic counselling to affected families to explain the implications for the patient and their relatives. Some considerations to take into account:
- Presymptomatic detection of relatives of an index case is important to allow early diagnosis.
- Pregnant women with early onset of the disease and under 40 years of age should be offered prenatal diagnosis through chorionic villus sampling.
- Genetic laboratory testing is not recommended for children under 18 years of age.
- The patient must sign an informed consent form prior to genetic laboratory testing; if the patient is a minor, a legal guardian must sign.
How is Andrade's disease treated?
Management of familial amyloid polyneuropathy must be multidisciplinary, involving a neurologist, geneticist, cardiologist and liver surgeon.
Liver transplantation is currently the only treatment to prevent the synthesis of amyloidogenic TTR variants. Liver transplantation can slow the progression of the disease in its early stages.
Symptomatic treatments are essential for autonomic sensorimotor neuropathies with visceral complications.
Request an appointment with us