Polineuropatía amiloidótica familiar en Mallorca. Reply / Familial amyloid polyneuropathy. Reply

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[Domino or sequential liver transplantation. Is it a feasible technique?]. / El trasplante hepático dominó o secuencial, es una técnica factible?

BACKGROUND: In domino liver transplantation (LT), the explanted liver of a patient with familial amyloidotic polyneuropathy (FAP) is donated to another patient. PATIENTS AND METHOD: Between February 1999 and March 2001 we performed 131 LT with 121 cadaveric donors in our unit. Ten domino LTs were performed. RESULTS: Patients with FAP were younger (37 years) than recipients of the second LT (64 years). The evolution of patients undergoing transplantation for FAP was excellent and all are currently alive and without complications. Among recipients of the second LT, one patient died in the postoperative period. A further two patients died from tumoral recurrence and hepatitis C virus recurrence 18 months and 9 months after transplantation, respectively. The remaining patients have shown no symptoms of FAP during the follow-up. CONCLUSION: The results of this study show that domino LT is technically feasible. The technique increases the number of grafts without apparent risk either to the recipient with FAP or to the recipient of the latter's explanted liver.

Two Spanish sibs with familial amyloidotic polyneuropathy homozygous for the V30M-TTR gene.

Two Spanish sibs with familial amyloidotic polyneuropathy (FAP) homozygous for the V30M-TTR gene, were diagnosed by DNA and protein analyses. Their clinical picture was very similar to the Majorcan FAP heterozygous patients except for the sensorimotor syndrome which was more aggressive. Noteworthy were clinical differences between the sibs concerning autonomic involvement, cranial neuropathy and kidney disturbances. These differences can be due to genetic and/or environmental factors.

[Sequential liver transplantation: description of the first three patients in Spain]. / Trasplante hepático dominó o secuencial: descripción de los tres primeros pacientes en España.

BACKGROUND: Domino or sequential liver transplantation (DTXL) is a kind of living donor transplant, which was proposed in 1993 and performed for the first time in 1995; later on, more than 45 have been reported. The liver from a patient with familial amyloidotic polyneuropathy(FAP) is used to another patient aged more than 60 with hepatic disease generally cancer, because FAP livers are anatomically and functionally normal except for the synthesis of the systemic TTR variant which only could generate FAP in the recipient after more than 8 years. PATIENTS AND METHOD: The three first cases of DTXL performed in Spain are presented. The donors were FAPTTRMet30 patients from the Major can focus. The first recipient showed severe hyperinsulinism due to metastatic liver from malignant insulinoma; the others had hepatocellular carcinoma on a cirrhotic liver. RESULTS: During the post operatory period liver function of recipients was perfect,and hyperinsulinism disappeared in the first; this patient died after 10 days by sepsis whereas the others showed normal liver function, no recurrent cancer nor onset of FAP. The donors outcome was normal with perfect liver function. CONCLUSIONS: Based on our results, in agreement with previous reports, we conclude that DTXH is valid procedure for a selected patient group. In addition they increase the pool of liver donors and therefore diminish the overloaded waiting lists.

Vitreous amyloidosis after liver transplantation in patients with familial amyloid polyneuropathy: ocular synthesis of mutant transthyretin.

Vitreous amyloidosis has been reported in patients with familial amyloidotic polyneuropathy (FAP) who are carriers of different mutant transthyretins (TTR). The mutant TTR constitutes the majority of the amyloid vitreous fibrils in heterozygous Val30Met patients. Due to the ocular synthesis of TTR, it is possible that the retina constitutes the source of vitreous amyloid fibrils, if so, orthotopic liver transplantation (OLT) performed to remove the mutant TTR from circulation might not be effective in treating/avoiding vitreous amyloid. We present vitreous amyloidosis in a FAP patient from Maiorca with ATTR Val30Met who underwent OLT at age 38. Progressive impairment of visual acuity (VA) appeared bilaterally 2 years after OLT due to vitreous opacities consistent with amyloid; successful bilateral vitrectomy was performed. Amyloid was demonstrated in the vitrectomy material by Congo red staining, immunohistochemistry and Western blotting analyses were positive with an antibody for human TTR. Mass spectrometry of TTR revealed the presence of the mutant in approximately 20% of the TTR. Future structural studies on vitreous material with different proportions of normal/versus mutant TTR might shed some light on TTR fibrillogenesis. These results show that vitreous deposition of TTR amyloidfibrils occurs after OLT, suggesting that ongoing intraocular synthesis of mutant TTR might contribute to this process. We also present the progression after OLT of vitreous amyloidosis previously diagnosed in three patients with TTR Val71Ala.

Two pairs of proven monozygotic twins discordant for familial amyloid neuropathy (FAP) TTR Met 30.

Twin studies are an important tool in medical genetics for the evaluation of the relative roles of genetic and non-genetic factors in several diseases. Familial amyloidotic polyneuropathy type I (FAP-I), TTR Met 30, was present in two sets of proven monozygotic (MZ) twins, one from Majorca and the other from Portugal. Monozygosity was established by analysis of DNA polymorphisms. Both pairs were discordant for age at onset and some clinical manifestations of FAP-I. We reviewed the differences in age at onset and clinical features in both sets and in two other pairs of presumed MZ twins with FAP-I and compared them with those in MZ twin pairs with other Mendelian disorders, such as neurofibromatosis type 1, Huntington's disease, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. We conclude that, in addition to the postulated modifying genes, there must be a significant contribution from non-genetic factors to the phenotypic variability of FAP-I (age at onset and clinical expression), either because of environmental differences or stochastic events during (or after) the twinning process.

[Corino Andrade disease]. / Enfermedad de Corino Andrade.

Familial amyloidotic polyneuropathy (FAP) or Corino Andrade disease, is a very frequent amyloidosis but little known. We summarized the epidemiologic and clinical aspects of the Majorcan patients diagnosed since 1976, which constitute the fifth worldwide endemic focus of this degenerative disease, and we reported the scientific advances on FAP which are the basis to control this redoubtable degenerative process: easy diagnosis of patients and asymptomatic carriers, etiopathogenetic treatment and genetic counseling to reach the eradication. FAP must be better known because of the progressive incidence in Spain and varied symptomatology, to avoid confusions with other neurologic or extra-neurologic diseases.

Long-term results of liver transplantation in familial amyloidotic polyneuropathy type I.

BACKGROUND: The aim of this article is to report our experience regarding the survival and the evolution of polyneuropathy of the extremities and autonomic dysfunction in 18 liver transplant patients with familial amyloidotic polyneuropathy type I after a mean follow-up of more than 2.5 years for 13 patients. METHODS: The actuarial survival rate of the 18 patients is 72.2% and 60.1%, respectively, at 12 and 58 months. RESULTS: In all the patients we noted clinical improvement of the polyneuropathy of the extremities and autonomic dysfunction during the first 6 months after transplant. The clinical data due to autonomic nervous system involvement showed an earlier improvement than those due to nervous motor involvement. CONCLUSIONS: In conclusion, our results suggest that liver transplant may be useful in the treatment of certain cases of familial amyloidotic polyneuropathy to stop the neurological deterioration of the patients and to avoid the fatal end of the disease.

Clinical improvement after liver transplantation for type I familial amyloid polyneuropathy.

Long-term results of 13 liver transplantations in patients with a previous diagnosis of type I familial amyloid polyneuropathy (FAP) are presented. The diagnosis of type I FAP was based on the presence of a biochemical marker in the plasma (TTR-Met-30 in 11 patients, TTR-Ala-71 in two). Maximum follow-up is 28 months and the survival rate stands at 11 of 13 patients. Two patients died from sepsis at 2 and 6 months. TTR disappeared from plasma in all cases. Neurological status improved in all eight patients undergoing transplantation more than 6 months previously, although electromyographic studies showed a slight improvement only in the six with follow-up of more than 1 year. All 13 patients showed a hyperdynamic haemodynamic pattern with a high incidence (four patients) of the use of venovenous bypass due to haemodynamic intolerance. Two patients also received transplants by the 'piggy-back' technique. In conclusion, liver transplantation may be useful in the treatment of certain patients with FAP to halt and improve the neurological consequences of the disease.

[Liver transplantation for the treatment of type I familial amyloidotic polyneuropathy]. / Trasplante hepático para el tratamiento de la polineuropatía amiloidótica familiar tipo I.

The first liver transplantation carried out in Spain for the treatment of type I familial amyloidotic polyneuropathy (FAP I) is presented. The reason for the operation was based on the liver being responsible for the synthesis of abnormal transtirretin (TTR) constituting the peculiar amyloid of the disease. Following transplantation a rapid and noticeable decrease in abnormal TTR was observed and the evolution of the clinical picture after 18 months of surgery is favorable with progressive improvement of the neurologic symptoms and normal function of the graft. These encouraging results coincide with those of the Swedish group of Umea, the pioneer of this procedure.