Familial Amyloidotic Polyneuropathy: domino liver transplantation

The primary cause of Familial Amyloidotic Polyneuropathy is a variant transthyretin gene on chromosome 18. Progressive polyneuropathy followed by fatal cardiac and renal failure commonly manifest during middle age. Within 10 years after onset of clinical symptoms, affected individuals usually die due to malnutrition or heart failure. Currently, liver transplantation is the only available therapeutic option.

We performed liver transplantation in two patients with Familial Amyloidotic Polyneuropathy carrying the transthyretin-30 mutant. Two patients aged more than 50 years received the two explanted amyloidotic livers. This procedure is called Domino liver transplantation. We report the outcome in the studied subjects and analyze the metabolic consequences of this procedure.

We determined the serum half-life of transthyretin-30 as 2.25 days using daily monitoring of transthyretin-30 levels. An affected amyloidotic patient had an increased serum concentration of lipoprotein(a) of 78 mg/dl before transplantation. The tumor patient, who received the organ from this affected patient, developed an almost identical serum concentration of lipoprotein(a) after liver transplantation, confirming the liver as the primary site of synthesis of this lipoprotein.

Once Domino liver transplantation has been performed, the impact of the liver-dependent metabolism of specific proteins of interest can be studied.