-
[show abstract]
[hide abstract]
ABSTRACT: Familial amyloidotic polyneuropathy (FAP) is a monogenic disease caused by mutations in the transthyretin (TTR) gene. The phenotype of the most common TTR mutation, V30M, varies within and between populations. Oxidative stress and protein misfolding are cellular processes involved in the development of FAP. Because the mitochondria are important for both these processes, we investigated if mitochondrial haplogroups are related to age at onset of the disease in Swedish and French FAP patients. Mitochondrial haplogroup analysis was performed on 25 early-onset (below 40 years) and 29 late-onset (above 51 years) Swedish FAP patients. DNA from 249 Swedish individuals served as controls. In addition, 6 early-onset and 17 late-onset French FAP patients were examined with 25 French controls. The haplogroup distribution among late-onset Swedish and French cases was similar to that found in the general populations, whereas among early-onset cases a different haplogroup distribution was seen. The relatively rare haplogroup K was significantly more common among early-onset cases. Our findings substantiate the suggestion that a genetic component, still to be found, affecting mitochondrial function has an impact on the amyloid generating process in transthyretin amyloidosis.
Clinical Genetics 12/2008; 75(2):163-8. · 3.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Since oxidative stress has been implicated in amyloid diseases, a study of scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23 familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a liver transplantation for the disease. Twenty patients completed the 6-month study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They were evaluated clinically and by immunohistochemical measurement of hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For non-transplanted patients, no improvement was found for HNE in relation to the amyloid content in biopsy specimens, whereas a tendency to a decreased amount was noted for transplanted patients. Clinically, no differences were found for non-transplanted patients, but an increased nutritional status, measured by a modified body mass index (mBMI) was noted for transplanted patients. In summary, scavenger treatment with the drugs and doses used in the present study appears to be unable to decrease lipid peroxidation in amyloid-rich tissue in non-transplanted FAP patients. For transplanted patients, lipid peroxidation tended to decrease, and the nutritional status measured by mBMI improved, even though the findings may be explained by liver transplantation alone, scavenger treatment may facilitate recovery after transplantation.
Scandinavian Journal of Clinical and Laboratory Investigation 03/2001; 61(1):11-8. · 1.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gastrointestinal disturbances are important prognostic factors for mortality and morbidity after liver transplantation for familial amyloidotic polyneuropathy (FAP). However, the impact of liver transplantation on malabsorption and bacterial small-bowel contamination has not been evaluated.
Twenty-three FAP patients were available for the study. They were examined for gastrointestinal disturbances as a part of the evaluation for liver transplantation for FAP. Bile acid malabsorption was diagnosed with the [75Se]-homocholic acid taurate (SeHCAT) test; fat malabsorption by measuring faecal fat excretion; and bacterial small-bowel contamination with the hydrogen breath test (HBT).
No significant improvement of malabsorption test results were noted from the pre-transplant evaluation 8 months (range, 2-20 months) before transplantation to the post-transplant evaluation performed a median of 20 months (range, 9-62 months) after the procedure. The SeHCAT test result became abnormal in two patients and normal in one, and changes in the test correlated with the time the patients were waiting for transplantation. Faecal fat excretion after transplantation correlated with duration of the disease and with fat excretion before transplantation. A significantly increased fat excretion was noted at the post-transplant evaluation. A change in HBT result was noted in only one patient, in whom the test result became normal; pre-transplant values correlated with those obtained after transplantation.
For most FAP patients no improvement in gastrointestinal function was found after transplantation. The finding underlines the importance of an early transplantation before the patients have developed gastrointestinal dysfunction.
Scandinavian Journal of Gastroenterology 10/2000; 35(9):985-9. · 2.02 Impact Factor
