Variant transthyretin in blood circulation can transverse the blood-cerebrospinal barrier: qualitative analyses of transthyretin metabolism in sequential liver transplantation

BACKGROUND: Although the choroid6 plexus of the brain is one of the most important production sites of transthyretin (TTR), the metabolism of TTR secreted in cerebrospinal fluid (CSF) remains to be elucidated. METHODS: To perform qualitative analysis of variant TTR in CSF of patients who underwent a sequential liver transplantation using an explanted familial amyloidotic polyneuropathy (FAP) ATTR Val30 Met patient's liver, levels and forms of TTR of the two patients were analyzed by means of enzyme linked immunosorbent assay (ELISA) and matrix-assisted laser desorption/time-of-flight mass spectrometer (MALDI/TOF-MS), respectively. RESULTS: After the operation, variant TTR levels in serum increased, and in CSF, a significant peak of free form of ATTR Val30 Met was detected in the transplanted patients whose CSF had shown no variant TTR before the operation. CONCLUSIONS: These findings suggest that the variant TTR can cross-the blood-CSF barrier and migrate into CSF from blood circulation. Because leptomeningeal amyloidosis occurs in FAP ATTR Val30 Met as the progression of the disease, this information suggests that in addition to peripheral neuropathy, disorders of the central nervous system (CNS) should be given an attention in patients who underwent sequential liver transplantation using an explanted FAP ATTR Val30 Met patient's liver.     

Presence of autoantibody against ATTR Val30 Met after sequential liver transplantation

BACKGROUND: Recently, sequential liver transplantation has been performed with an explanted liver from a patient with familial amyloidotic polyneuropathy (FAP) because of the shortage of donors. However, metabolism of amyloidogenic transthyretin (ATTR), the pathogenic protein of FAP, has not been well studied in patients who have undergone sequential liver transplantation. The purpose of this study was to examine the changes in serum ATTR levels and to investigate the presence of an autoantibody in patients who underwent sequential liver transplantation with an explanted organ from a patient with heterozygotic FAP (FAP ATTR Val30Met). METHODS: This was a case study performed at the Kumamoto University School of Medicine, Kumamoto, Japan, and Kyoto University School of Medicine, Kyoto, Japan. Intervention occurred by sequential liver transplantation with an explanted FAP patient's liver. Levels of normal TTR and ATTR in the two patients who received the transplanted liver were analyzed by means of an enzyme-linked immunosorbent assay (ELISA) and a matrix-assisted laser desorption/time-of-flight mass spectrometry. In addition, the presence of an autoantibody against ATTR Val30Met was evaluated via ELISA using purified ATTR Val30Met from homozygotic FAP patients' sera. RESULTS: After the operation, the variant TTR levels were unexpectedly lower than levels of normal TTR in serum samples from patients with a transplanted liver from the FAP patient. An autoantibody against the variant TTR was detected on day 3 after the operation in the serum of those patients and continued to be present for at least 2 months after the operation. CONCLUSIONS: An autoantibody against the variant TTR may reduce the serum levels of variant TTR. Although the antibody may play a beneficial role in reducing the pathogenic protein, the long-term effect of the antibody must be investigated further.     

Manifestations of transthyretin-related familial amyloidotic polyneuropathy: Long-term follow-up of Japanese patients after liver transplantation

Purpose

To observe which symptoms of transthyretinrelated familial amyloidotic polyneuropathy (FAP) progressed in the long term after liver transplantation (LT), focusing on cardiac, kidney, and ocular symptoms.

Methods

We reviewed the medical records of 34 Japanese patients with FAP, who underwent LT between 1994 and 2006. The mean follow-up period (±SD) after LT was 9.6 ± 3.4 years. Of the 34 patients, 30 had FAP amyloidogenic transthyretin (ATTR) Val30Met, 1 had FAP ATTR Ser50Ile, and 3 had FAP ATTR Tyr114Cys.

Results

The 10-year survival rates from the onset of FAP and from the time of LT were 100% and 91.4%, respectively. Progression of ocular amyloidosis was seen in 17 (50%) patients, 13 of whom had de novo amyloid deposits in the vitreous body; progression of cardiac amyloidosis was seen in 10 (29%) patients, 4 of whom had newly granular sparkling echo on echocardiography, and 9 of whom had newly implanted pacemakers or implantable cardioverter-defibrillators. Although the mean serum creatinine levels did not increase significantly after LT in any of the patients, the estimated glomerular filtration rate had decreased significantly by 7 years after LT.

Conclusion

Although LT is life-saving for patients with FAP, we observed progression of the ocular and cardiac symptoms of FAP in a significant number of these patients over the long term after LT.     

Transthyretin-derived amyloid deposition on the gastric mucosa in domino recipients of familial amyloid polyneuropathy liver.

Familial amyloid polyneuropathy (FAP) is a form of hereditary generalized amyloidosis. Liver tissue explanted from FAP patients has normal structure and function, except for the production of amyloidogenic variant transthyretin (TTR), and domino liver transplantation (DLT) using grafts from FAP patients was first performed in 1995. FAP symptoms usually develop in genetically determined individuals after the age of 20, but it is difficult to estimate when FAP symptoms will appear in domino recipients. Concerning this problem, histological findings showing amyloid deposition have recently been obtained in a few domino recipients of FAP livers. This study investigated the presence of de novo amyloid deposition in the gastroduodenal mucosa of domino recipients transplanted at our institution. Biopsy of gastroduodenal mucosa was carried out in 5 recipients of FAP livers and TTR-derived amyloid deposits were detected in 2 patients, both of whom had undergone DLT 47 months previously. In FAP liver recipients, de novo systemic amyloid deposition may begin much sooner than previously supposed. Therefore, careful follow-up of domino recipients of FAP livers is required.     

Liver transplantation for hereditary transthyretin amyloidosis

Transthyretin (TTR) amyloidosis is the most commonform of hereditary amyloidosis. It is a systemic amyloidosis caused by an amyloidogenic variant TTR (ATTR), of which the methionine for valine at position 30 (ATTR Val30Met) gives rise to a fatal neuropathic amyloidosis. Because more than 95% ofTTR is produced by the liver, a liver transplantation should abolish the liver's production of amyloidogenic mutant TTR and thereby halt amyloid formation. The first liver transplantation for hereditary TTR amyloidosis was performed in Sweden in 1990 on a patient with ATTR Val30Met amyloidosis, and the result was encouraging. Today, liver transplantation for TTR amyloidosis is an established treatment. However, the disease is rarely seen except in a few endemic areas; therefore, most transplantation centers only receive a few cases. Because the disease phenotype varies with different TTR mutations and variability is even encountered for the same mutation, an evaluation of patients for transplantation must include an investigation of all organs that may be affected by the disease and may impact on the morbidity and mortality of the procedure. The aim of this review is to present the results of liver transplantation for TTR amyloidosis and give recommendations for patient evaluation and selection based on the literature and our experience with the disease.     

Familial amyloid polyneuropathy type I (Portuguese): distribution and characterization of renal amyloid deposits

Renal amyloidosis has been considered rare and late in the evolution of the transthyretin (TTR) familial amyloid polyneuropathy (FAP) of the Portuguese type (type I). Renal biopsy has been performed systematically in 14 patients with FAP type I before liver transplantation. In all patients, TTR Met30 mutation was shown. Seven had proteinuria or abnormal microalbuminuria, whereas seven others had no urinary abnormalities. All had renal amyloid deposition predominantly in the medulla. Glomerular and vascular involvement was more prominent in patients with urinary abnormalities. Patients with the most extensive renal lesions represented a subgroup with a low score of polyneuropathy disability, a high prevalence of nephropathy in the proband generation, or a late onset for relatives with nephropathy. Immunohistochemistry studies showed that the amyloid substance corresponded to transthyretin. We have shown that renal TTR-derived amyloid deposition is common in patients with FAP type I, even in the absence of urinary abnormalities. The clinical presentation of nephropathy is not a late occurrence in the disease.     

Prevalence of germline mutations in the TTR gene in a consecutive series of surgical pathology specimens with ATTR amyloid

Transthyretin-derived amyloidosis (ATTR) amyloidosis is the third most prevalent amyloid type in surgical pathology and may occur as a hereditary disease with germline mutations in the TTR gene or as senile systemic amyloidosis (SSA) without mutations. Distinction between hereditary ATTR amyloidosis and SSA is of central importance, as the former necessitates genetic counseling and can be treated by liver transplantation. However, little is known about the prevalence of hereditary ATTR amyloidosis in surgical pathology specimens. We have examined the distribution of hereditary ATTR amyloidosis and SSA in a consecutive series of surgical pathology specimens with histologically and immunohistochemically confirmed ATTR amyloid. Thirty-three consecutive patients were retrieved from the Amyloid Registry of the Charité University Hospital. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tissue or patient blood and examined by DNA sequencing. ATTR amyloid was found in the gastrointestinal tract, endomyocardium, peripheral nerve, carpal tunnel ligament, synovia, breast, and testicle. Amyloid fibrils were present as interstitial and vascular deposits, as evidenced by Congo red staining. TTR gene mutations were detected in 12 of 30 patients, with p.Val30Met being the most prevalent (5 patients). Furthermore, 2 novel mutations (p.Asp39Val and p.Glu54Asp) were found. In patients carrying a mutation, ATTR amyloid was found in the gastrointestinal tract, myocardium, nerve, and testicles. To conclude, the hereditary form of ATTR amyloid seems to be more common in elderly patients than previously thought. It is, therefore, important to genetically test every patient when diagnosing ATTR amyloidosis.     

Sequential (domino) transplantation of the liver in a transthyretin-50 familial amyloid polyneuropathy

Background: General shortage of cadaveric organs has led to a search for alternative methods to expand the donor pool. Sequential (domino) transplantation is yet another attempt to compensate for the declining consent to organ donation. Patients and methods: To qualify for a domino liver transplantation, the following preconditions must be fulfilled: (1) extrahepatic disease must exist, (2) liver must be fully functional, and (3) the genetic defect in the host should recur within a sufficient latency period. Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease which involves a genetic defect for transthyretin (TTR), which is predominantly produced in the liver. Results: In this report, we describe a rare case of a FAP TTR-50 variant undergoing domino liver transplantation. Since myocardial symptoms precede peripheral polyneuropathy, special emphasis should be placed on arrhythmias and the restrictive cardiomyopathy necessitating a veno-venous bypass or a cardiac pacemaker in order to improve cardiac contractility. The type of anastomosis of the suprahepatic inferior vena cava and possible alternatives are discussed. Conclusion: Despite ethical problems, the advantages of the domino procedure are obvious: (1) expansion of the donor pool, (2) ability to use living donors, and (3) presence of very short ischemic time and thus excellent liver function. Due to the kinetics of TTR production and deposition, donors and recipients of FAP livers should be followed up using an extensive neurological and cardiological protocol. Received: 15 June 1999 Accepted: 12 November 1999     

Effect of tacrolimus and partial hepatectomy on transthyretin metabolism in rats

Liver transplantation, which serves as treatment of familial amyloidotic polyneuropathy (FAP), and domino liver transplantation, which utilizes resected livers from patients with FAP for treatment of liver diseases, may induce changes in transthyretin (TTR), a pathogenic FAP-related protein. To evaluate this possibility, we performed a 70% hepatectomy or administered tacrolimus to Dark Agouti (DA) rats for 7 days and then measured changes in liver TTR mRNA levels and changes in serum TTR concentrations. After hepatectomy, TTR mRNA levels decreased by 77%; at day 3, they returned to preoperative levels. Except for slightly elevated serum TTR concentrations 12 h after operation, serum TTR levels remained unchanged. Thus, partial hepatectomy did not influence serum TTR concentrations. After tacrolimus administration, TTR mRNA declined by 56% 12 h after the experiment started; however, after day 3, a rebound phenomenon occurred until day 7. Tacrolimus may facilitate serum TTR degradation, although production of TTR in the liver also increased. This finding -- that TTR, the source of FAP-inducing amyloid, did not increase after transplantation -- may help post-transplantation treatment of patients who have FAP and other liver diseases.     

Corino-andrade disease (familial amyloidotic polineuropathy type I) in Spain: Urological and andrological disorders

In our hospital, we have followed a group of patients with familial amyloidotic polyneuropathy (FAP), type I. This disease is characterized by a progressive sensitive-motor and autonomic polyneuropathy. The amyloid fibrils of FAP I contain a mutant transthyretin (TTR) molecule. More than 90% of TTR production occurs in the liver. Thus, therapy with liver transplantation has proved useful. All our patients received this treatment. In this study we describe the urological and andrological disorders caused by FAP type I in 12 patients with low bladder pressure and bladder neck obstruction with micturition disorders. In some males, it was accompanied by impotence and retrograde ejaculation produced by autonomic neuropathy. We believe hepatic transplantation may be the best treatment for this disease.     

No ocular involvement in familial amyloidotic polyneuropathy ATTR V30M domino liver recipients

In many transplantation centers domino liver transplantation is an established procedure, increasing the number of available liver grafts. Increasingly, grafts from familial amyloidotic polyneuropathy (FAP) patients are used. Ocular involvement is a well known manifestation of FAP, and can be vision-threatening. The aim of this study was to evaluate the risk of development of familial amyloidotic polyneuropathy ocular manifestations in domino liver recipients. Forty-four cirrhotic patients submitted to liver transplantation were studied, with an average of 6 years of follow up after the procedure. Twenty two patients had received a liver from a FAP donor (Group 1) and 22 had received a liver from a non-FAP cadaveric donor (Group 2). Both groups were similar for mean age and gender. Routine ophthalmological examinations with particular attention to amyloid deposition in the anterior segment and vitreous, peripheral retina state, lacrimal functions tests (Schirmer and tear break-up time) and pupillometry (dynamic and static) were performed. No statistically significant differences were observed in all studied ophthalmic parameters between the two groups. No FAP related ophthalmic manifestations were detected after 6 years of domino liver transplantation, but further prospective regular ophthalmological examinations are necessary to detect the eventual development of late ocular manifestations.     

Portuguese-type amyloidosis (transthyretin amyloidosis,ATTR V30M)

Portuguese-type amyloidosis (transthyretin amyloidosis, ATTR V30M) is the most common form of systemic hereditary amyloidosis, inherited in autosomal dominant mode. The disease, also called familial amyloid polyneuropathy type I (FAP-I), is caused by a mutant transthyretin (TTR) protein, which is synthesized by the liver. A single amino acid substitution of methionine for valine at position 30 of the TTR molecule (TTR V30M) was found in Portuguese patients. The clinical disease usually manifests as a peripheral sensory, motor and autonomic neuropathy starting in the 3rd or 4th decade of life. Renal manifestations of ATTR V30M, like other amyloidoses, are different levels of proteinuria and renal insufficiency. In ATTR V30M a large amyloid deposition in the medullary zone of the kidney and tubules is characteristic. A more extensive glomerular and vascular involvement is present only in patients with renal manifestations. A prospective survey in the north of Portugal showed that a stage of microalbuminuria (MA) could precede nephropathy and neurological disease. Nephropathy in FAP-I is present in one-third of affected patients and tends to aggregate in families. The progression towards end-stage renal disease (ESRD) affects 10% of the patients, and the survival after initiation of dialysis is a mean of 21 months. Patients who progress to ESRD have a late onset of neuropathy and lower prevalence of clinical disease in their families. Liver transplantation is a widely accepted treatment for FAP-I, and combined liver-kidney transplantation is also an option for selected patients with FAP-I and ESRD.     

Progressive Wild-Type Transthyretin Deposition after Liver Transplantation Preferentially Occurs onto Myocardium in FAP Patients

To elucidate whether progressive wild-type transthyretin (TTR) deposition can actually occur after liver transplantation (LT), amyloid fibrils were investigated in two familial amyloid polyneuropathy patients with TTR Val30Leu variant, who died 1 year after LT. Amyloid fibrils were extracted from cardiac muscles, sciatic nerves and kidney, which were investigated by the immunoprecipitation-mass spectrometry method and liquid chromatography-ion trap mass spectrometry analysis. The ratio of wild-type to variant TTR in cardiac muscle was approximately 5:5 before LT, but greatly increased to about 9:1 after transplantation. The ratios in sciatic nerves and kidney obtained at autopsy were approximately 5:5. Wild-type TTR was undetectable in kidney amyloid obtained before LT. Our results indicate that paradoxical wild-type TTR deposition after LT can preferentially occur in myocardium, leading to fatal cardiac dysfunction, but it is quite likely that this phenomenon can also occur in other visceral organs.     

Ten years of international experience with liver transplantation for familial amyloidotic polyneuropathy: results from the Familial Amyloidotic Polyneuropathy World Transplant Registry

BACKGROUND: Transthyretin (TTR) amyloidosis is a group of systemic amyloidoses disorders caused by an amyloidogenic TTR variant. Untreated, it slowly leads to severely disabling symptoms that relentlessly progress until the death of the patient. Because the mutant form of TTR is produced mainly in the liver, successful orthotopic liver transplantation (OLT) results in the elimination of the source of the variant TTR molecule and is presently the only known curative treatment. OLT in patients with familial amyloidotic polyneuropathy (FAP) was first performed in 1990 at the Karolinska Institute in Sweden, and because the results were promising other centers took up the procedure. METHODS: To gain as great an experience as possible regarding this treatment, the Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR) was initiated in 1995, and this article presents the 10-year registry results. RESULTS: A total of 54 centers in 16 countries have performed OLT for FAP, and today approximately 60 OLTs are performed annually worldwide. During the last decade, a total of 539 patients have undergone 579 OLTs. Patient survival is excellent (overall 5-year patient survival 77%) and comparable to the survival with OLT performed for other chronic liver disorders, but longer follow-up is needed to compare the outcome after OLT with the natural course of the disease. The main cause of death was cardiac related (39%). CONCLUSIONS: We believe that the FAPWTR has become a valuable tool that will help to accurately evaluate the potential risks and benefits of OLT in patients with FAP and promote a fruitful collaboration between centers engaged in this field.     

Changes in renal function in patients with familial amyloid polyneuropathy treated with orthotopic liver transplantation.

BACKGROUND: Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease caused by a point mutation in the gene encoding transthyretin, which is secreted by the liver. Orthotopic liver transplantation (OLT) has been proposed to prevent disease progression. Little is known about long-term changes in renal function and lesions after OLT. METHODS: The renal function of 33 patients with FAP was evaluated (proteinuria, serum creatinine, creatinine clearance) before OLT and over a period of at least 5 years afterwards. A pre-transplantation renal biopsy was performed in 14 patients and a follow-up biopsy in eight patients. RESULTS: Before transplantation, mean serum creatinine concentration was 86 micromol/l (47-126 micromol/l) and creatinine clearance was 71.9+/-31.6 ml/min/1.73 m(2). Proteinuria was detected in 54% of patients (0.3-4 g/day). Pre-transplant renal biopsies (n = 14) revealed glomerular, tubular and vascular amyloid deposits in 90, 58 and 66% of patients, respectively. Eleven patients (33%) died after OLT. Death occurred most frequently in patients having weight losses >7 kg (P<0.05). After transplantation, 25 patients (76%) suffered acute renal failure but only one required dialysis. One month after transplantation, the mean serum creatinine concentration was 134.1+/-73 micromol/l and remained constant during follow-up. Eight patients underwent a second renal biopsy 2 years after transplantation. No significant changes in deposits or renal toxicity due to calcineurin inhibitors were detected. CONCLUSION: Although liver transplantation in FAP does not affect existing renal amyloid deposits, it prevents the progression of renal disease.     

Long-term follow-up of survival of liver transplant recipients with familial amyloid polyneuropathy (Portuguese type)

Portuguese type familial amyloid polyneuropathy is a dominantly inherited neuropathic amyloidosis caused by a mutant transthyretin (TTR). Because TTR is produced mainly by the liver, liver transplantation (LT) abolishes production of the amyloidogenic variant TTR. To date, the procedure appears to halt the progress of the disease. However, long-term outcome is unknown. The aim of the present study is to evaluate the survival of our initial group of unselected liver transplant recipients with FAP. Seventy patients, 51 transplant recipients and a control group of 19 nontransplantation patients, with disease onset before the age of 55 years were included on the study. Transplant recipients were divided into two categories: (1) early series, with patients followed up for 5 years or longer, and (2) new series, with patients followed up for 1 to 5 years. Nonparametric statistical methods were used. Binary regression analyses were performed by stepwise logistic regression and Cox proportional hazard regression. Survival analysis was performed using Kaplan-Meier analysis, the Cox-Mantel test. Survival analyses and Cox proportional hazard regression analysis were performed from disease onset, not from LT. Significantly decreased survival was noted for transplant recipients with a modified body mass index (mBMI) less than 600 compared with the control group (P < .05). A significant difference in survival also was observed between transplant recipients with an mBMI greater than 600 at the time of LT compared with those with an mBMI less than 600 (P < .02). mBMI and age at LT had a significant impact on survival; whereas late deaths were related to age at LT, early deaths were related to mBMI. The cumulative 10-year survival rate after disease onset was 94% in the new series, with one early death (<6 months) after LT, compared with a 78% survival rate and eight early deaths in the early series (P = .1). (Liver Transpl 2002;8:787-794.)     

Characterization of end-stage renal disease after liver transplantation in transthyretin amyloidosis (ATTR V30M)

Transthyretin (TTR) amyloidosis, an autosomal-dominant disease, is characterized by peripheral and autonomic neuropathy—familial amyloidotic polyneuropathy (FAP). End-stage renal disease (ESRD) occurs at 10 years after the onset of neuropathy. Orthotopic liver transplantation (OLT) is the usual treatment of choice. We evaluated FAP patients, ATTR V30M, before and after OLT who started dialysis within 3 months after surgery. The 11 patients had an age at the onset of neuropathy of 31.9 ± 6.3 years with a mean evolution of disease to OLT of 4.54 ± 2.5 years. The glomerular filtration rate was <60 mL/min in 2 patients, 2 displayed nephrotic range proteinuria, and 3 had microalbuminuria. Elective pacemaker implantation was necessary in 8 subjects. Post-OLT 3 patients developed proteinuria, 2 of whom showed increasing nephrotic syndrome. Dysautonomia worsened leading to bladder catheterization in 6. In patients with previous normal renal function and proteinuria <3 g/d, the evolution of neuropathy to the first dialysis was 14.6 ± 4.2 years versus 7.5 ± 1.1 among the other subjects. Overall, dialysis was implemented at 7.4 ± 4.9 years after surgery. There was no liver graft dysfunction. The heart evaluation post-OLT showed the following: 3 patients with de novo dysrhythmias requiring pacemaker implantation and 3 with N-terminal pro-natriuretic peptide levels >10,000 pg/mL. Death occurred in 4 subjects at an average of 26 months after initiation of dialysis. Concerning ESRD, there was no clear benefit of transplantation in the early stages. Patients with normal renal function and lower levels of proteinuria showed slower progression to ESRD, irrespective of their duration of neuropathy.     

Liver transplantation in transthyretin amyloidosis: Characteristics and management related to kidney disease

Orthotopic liver transplantation (LT) was implemented as the inaugural disease-modifying therapy for hereditary transthyretin (ATTR) amyloidosis, a systemic amyloidosis mainly affecting the peripheral nervous system and heart. The first approach to pharmacologic therapy was focused on the stabilization of the TTR tetramer; following that new advent LT was assumed as the second step of treatment, for those patients whose neuropathy becomes worse after a course of pharmacologic therapy.The renal disease has been ignored in hereditary ATTR amyloidosis. The low level of proteinuria or slight renal impairment does not suppose such a heavy glomerular and vascular amyloid deposition. Moreover, severity of renal deposits does not consistently parallel that of myelinated nerve fiber loss. These are pitfalls that limit the success of LT and suggest troublesome criteria for pharmacological therapy or LT. An algorithm of evaluation concerning renal disease and treatment options is presented and some bridges-to-decision are exposed. In stage 4 or 5 kidney disease, the approach remains to deliver combined or sequential liver–kidney transplantation in eligible patients. However, in the majority, hemodialysis is the only option even in the presence of a well-functioning liver graft.In this review, we highlight useful information to aid the transplant hepatologist in the clinical practice.     

Heart Transplantation for Homozygous Familial Transthyretin (TTR) V122I Cardiac Amyloidosis

Heart failure is the usual cause of death in patients with amyloid cardiomyopathy. The commonest form of hereditary cardiac amyloidosis is associated with the Val122Ile variant of transthyretin (TTR), which is carried by 3–4% of the African American population. Here, we report the outcome of the first cardiac transplantation in a patient with TTR V122I. A 59-year-old Caribbean man presented with biventricular failure. Other than previous bilateral carpel tunnel syndrome, he had been well and had no evidence of extracardiac amyloidosis. An endomyocardial biopsy demonstrated amyloid of TTR type. Sequencing of TTR gene indicated homozygosity for V122I. He underwent cardiac transplantation and 3 years later, remains well with no evidence of allograft or systemic amyloid deposition.     

Serum potassium concentrations after suxamethonium in patients with familial amyloid polyneuropathy type I

Background: Suxamethonium produces an abnormal increase in serum potassium in some neurological diseases and some authors have suggested that it is safer not to use this drug in patients with familial amyloid polyneuropathy (FAP). However, there are no data previously reported to support this hypothesis. The aim of this study was to evaluate the magnitude of the potassium increase produced by suxamethonium in FAP type I.
Method: Twenty-one FAP Met 30 patients anaesthetised for liver transplantation were studied. Age was 34.9±6.9 years (mean± SD), time elapsed from first symptom 5.5 ±3.2 years and weight was 14±9% below ideal body weight. Anaesthesia was induced with thiopentone and low-dose fentanyl. Samples for blood gas and electrolytes analyses were drawn before induction and 1 and 5 min after 1 mg/kg of suxamethonium was given for tracheal intubation.
Results: Before induction serum potassium levels were 3.8±0.4 mmol/L. One minute after suxamethonium, values were 3.8±0.4 mmol/L and 5 min after 4.3±0.5 mmol/L. The maximal increase observed was 1.6 mmol/L (from 3.4 mmol/L to 5.0 mmol/L).
Conclusion: The average increase in plasma potassium concentrations observed in FAP patients after suxamethonium was similar to the increase observed in a normal population by others. Our study can exclude the hypothesis that an anomalous increase in potassium would be a typical and frequent response to suxamethonium in FAP Met 30 patients. However, we cannot exclude that a dangerous rise in serum potassium may exist in a certain percentage of FAP patients.