Until now, FAP associated with the Val30Met mutation is the best characterized form of the disease, probably because it is the most prevalent. Mutations in the TTR gene cause different clinical phenotypes for FAP, which can be more or less severe and particularly affect the peripheral nervous system, where neurodegeneration is initiated. During the development of the disease, other organs such as the kidneys and the heart can be affected.
Great phenotypic variability can be observed between families from different geographical origins, specially in relation to the age of onset, as well as to the penetrance of the disease and to the organs and tissues predominantly affected. This raises the possibility that other genetic and environmental factors may be involved in the pathophysiology of this disease.
FAP associated with mutations in the TTR gene (namely type I or Portuguese form) is of special importance for the Brazilian population, since it is the one found in Brazil due to the origin of our colonization.
The FAP was first described by the Portuguese neurologist Corino Andrade in 1952, who reported it as a specific and hereditary pathological condition, as addressed in his pioneering articles published in the early 1950s.
Studies using the Brazilian population show that the penetrance of FAP in Brazil is 83%, and the age of onset is around 30-40 years old, similar to what is observed for the Portuguese population. The V30M mutation is the most frequently described variant in the country, and the number of families affected by FAP is considerably growing.
Characterization of symptoms
Initially, the general symptoms are: foot pain, loss of sensitivity to temperature, numbness. Later, they evolve to also affect the upper limbs, and loss of another sensory modality (touch, sense of body position in space) can occur.
The motor involvement occurs late in the disease, initially in the lower limbs, progressing to atrophy and weakness, predominantly observed in the feet and legs. Involvement of the upper limbs occurs later. With the disease progression, osteo-tendon reflexes are usually lost.
The autonomic nervous system is commonly affected, which occurs early. Symptoms such as anisocoria (unequal pupil diameter), constipation, diarrhea, bloating, impotence, lack of sphincter control, severe postural hypotension, among others, indicate the involvement of the autonomic nervous system by the disease.
Another system frequently affected by Val30Met mutation-related FAP is the cardiovascular one. Cardiac involvement usually manifests in the form of heart rhythm disturbances, heart failure or blockages. Cardiomyopathy with thickened interventricular septum and ventricular walls can be evidenced in some patients by two-dimensional echocardiography.
Deposits of amyloid material in the vitreous (the viscous and jelly-like substance found under pressure in the posterior chamber between the crystalline lens and the retina, in order to maintain the spherical shape of the eye) were observed in patients with the Val30Met TTR mutation. It is an early manifestation in patients of Swedish origin.