TRANSTHYRETIN TYR77 FAMILIAL AMYLOID POLYNEUROPATHY - A CLINICOPATHOLOGICAL STUDY OF A LARGE KINDRED

More than 40 point mutations (producing different clinical manifestati ons) have been described in diverse points of the plasma protein trans thyretin (TTR). The Met30 is considered the most common mutation, the Tyr77 mutation being the second most prevalent. However, data from pat ients with this late mutation are scarce, and usually come from isolat ed case reports or tables. The Tyr77 mutation is not as well character ized as the Met30 mutation, especially with respect to such aspects as prognosis or possible treatment by liver transplantation. We therefor e present the clinical and pathological features of an extensive famil y with the Tyr77 TTR mutation, comprising 12 affected individuals over four generations. Six living individuals were followed over a 10-year period. Retrospective data were obtained with regard to the deceased family members. We found that an initial and sometimes prolonged carpa l tunnel syndrome, beginning between the 6th and 7th decades, characte rizes the Tyr77 mutation. In most cases this evolved to generalized pe ripheral nerve involvement, restrictive cardiomyopathy, and intestinal malabsortion. Although survival is usually high, there are progressiv e cases that should be candidates for liver transplant, before severe impairment has developed. (C) 1998 John Wiley & Sons, Inc.