A severe form of amyloidotic polyneuropathy in a Costa Rican family with a rare transthyretin mutation (Glu54Lys).

Four affected siblings in a Costa Rican family presented an aggressive polyneuropathy with widespread involvement of many visceral organs and onset during the third decade of life with rapid loss of muscle mass in the lower limbs and severe dysautonomy. The medical histories include vitreous opacity, cardiac enlargement, dermal and gastrointestinal infiltration, and autonomic dysfunction including circulatory compromise and gastrointestinal disturbances. Histological studies using Congo red stain and immunohistochemical assays with antibodies against the transthyretin (TTR) protein showed widespread deposition of amyloid in extracellular areas, including dermis and gastrointestinal lamina propia, endo- and perineural spaces, and vascular walls. A mutation search in the transthyretin (ttr) gene was performed seeking the cause of this severe form of familial amyloidotic polyneuropathy (FAP). We applied single-stranded conformational polymorphism (SSCP)-analyses followed by sequencing of the four exons of the ttr gene, revealing a point mutation in exon 3, a G to A transition that causes a Glu54Lys codon change. Western blots of plasma proteins incubated with anti-transthyretin antibodies after gel electrophoresis provided separation of wild-type and mutant TTR protein in affected family members.