Long-term results of liver transplantation in four siblings from the same family with familial amyloidotic polyneuropathy type I TTR Ala-71

Abstract

Familial amyloidotic polyneuropathy type I (FAP I) is a hereditary systemic amyloidosis usually involving the peripheral nervous system. In this paper we report our experience regarding the survival and the evolution of the sensory motor syndrome of the extremities and autonomic dysfunction in four siblings with the Ala-71 variant who were treated by liver transplantation (LT). The four siblings are alive 2-5 years after LT. After the operation, the seriated determinations of TTR-Ala-71 variant showed a constant decrease in serum levels in all cases. Our results support the proposal that LT should be indicated especially in forms with early clinical onset (3rd and 4th decades) and rapid progress to stop the neurological deterioration of the patients.

Liver transplantation for hereditary transthyretin amyloidosis

“…Good survival and symptomatic response were noted in a German patient with the ATTR Lys47Gly mutation, 90 and good results with regard to both survival and symptomatic improvement were reported from Spain in a series of 4 patients with the Val71Ala mutation. 91 However, the mortality rate has been high for other mutations, and progression of cardiac amyloidosis after liver transplantation has been reported 31,32,79,92 (Table 1). A combined liver and heart transplantation may be needed in several mutations, although progression of both cardiac amyloidosis and polyneuropathy were reported for the ATTR Ser77Tyr mutation from 1 center.…”

Liver transplant for inherited metabolic disease among siblings

“…There have only been two previously published case series describing siblings undergoing LT, along with several case reports of single families with multiple affected siblings. [5][6][7][8][9][10][11] Koljonen at al 5 including non adherence, poor quality of life, and psychological distress. 13 It seems intuitive that these burdens would be increased where multiple siblings are affected, but this has not been formally investigated.…”

“…In the discordant families, in one family the second sibling was transplanted at a younger age and in the other family they were older at LT. There are a number of case reports of siblings undergoing LT for a variety of IMD including Crigler-Najjar syndrome,9 familial hypercholesterolemia,11 familial amyloid polyneuropathy,7 and glycogen storage disease 8. All describe the experience of single families, most of whom underwent LT as adults.Neither this study or the published literature have addressed the psychosocial consequences for families of having multiple siblings requiring LT.…”

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“…3 Adult sibling liver transplant recipients generally had amyloid metabolic disturbances. 2,7,8 Other indications were related to altered cholesterol metabolism. 6 In our series, the indications for orthotopic liver transplant in pediatric cases were biliary cirrhosis, Wilson disease, hepatocellular Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; FFP, fresh frozen plasma; INR, international normalized ratio; PRBC, packed red blood cell; RRT, renal replacement therapy carcinoma, and hyperoxalosis; in adult cases, the indications were viral hepatitis and biliary cirrhosis.…”

“…Previous literature experience of liver or kidney transplant in siblings has disseminated mainly through case reports. [2][3][4][5][6][7][8] In pediatric cases, the indications for liver transplant were type IV glycogen storage disease, 4 familial hypercholesterolemia, 5 and Crigler-Najjar syndrome. 3 Adult sibling liver transplant recipients generally had amyloid metabolic disturbances.…”