Familial amyloid polyneuropathy (TTR ala 60) in north west Ireland: a clinical, genetic, and epidemiological study.
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A cluster of cases of familial amyloid polyneuropathy has been described in Donegal, north west Ireland. Two patients from this region have been shown to have the ala 60 mutation in the transthyretin gene. Three kindreds with this mutation have also been described in the United States. Genealogical and haplotype studies indicate that all known patients with this mutation are related and are descended from a founder in north west Ireland. There is evidence for reduced penetrance of this disorder. A population based study showed that 1.1% of the population in this area in north west Ireland carry the mutation. This has implications in terms of diagnosis, genetic counselling, and treatment in the future. (+info)
A new transthyretin variant (Ser 24) associated with familial amyloid polyneuropathy.
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An American kindred with systemic amyloidosis presenting with carpal tunnel syndrome, peripheral neuropathy, and cardiomyopathy is reported. The transthyretin gene of a patient was analysed by direct DNA sequencing and both cytosine and thymine were present at the first base of codon 24. This new point mutation in exon 2 results in the amino acid substitution of serine for proline in the A-B loop of the transthyretin molecule. DNA testing for this mutant allele by restriction fragment length polymorphism analysis based on the polymerase chain reaction is described. (+info)
Cardiac sympathetic denervation in transthyretin-related familial amyloidotic polyneuropathy: detection with iodine-123-MIBG.
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In familial amyloidotic polyneuropathy (FAP), the peripheral nervous system is predominantly impaired. Cardiac sympathetic function has not been directly assessed. A 65-yr-old man with severe peripheral neuropathy due to primary systemic amyloidosis was studied. Echocardiograms and scintigraphic examinations with 20Tl and 99mTc-pyrophosphate demonstrated highly thickened but normally perfused left ventricular walls with intense diffuse amyloid deposits. No definite myocardial activity of [123I]metaiodobenzylguanidine (MIBG) was detected in any cardiac region, indicating lack of sympathetic nerve endings. Despite maintained cardiac contractility, left ventricular diastolic performance and heart rate variability assessed by power spectral analysis were markedly depressed. Thus, the myocardial defect of MIBG activity may provide direct evidence of impaired cardiac sympathetic nerve endings due to amyloid deposits in FAP. (+info)
Treatment of a Japanese patient with familial amyloidotic polyneuropathy with orthotopic liver transplantation.
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A 28-year-old male patient with familial amyloidotic polyneuropathy (FAP) underwent a liver transplantation from a heart-beating cadaveric donor in Sweden. He had suffered from the disease for 2.5 years. It took 5.5 hours to carry out the operation without blood transfusion. After the liver transplantation, serum amyloidgenic variant transthyretin (TTR) levels became extremely low and diarrhea stopped after the 7th day. On day 13, the patient was discharged from the hospital and one month after the transplantation, his general condition remained quite good. This is the first case of a Japanese patient with congenital metabolic disorders as well as FAP to receive a liver transplantation from a heart-beating cadaveric donor. (+info)
Molecular diagnosis of transthyretin Met30 mutation in an Italian family with familial amyloidotic polyneuropathy.
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We report the molecular analysis of the transthyretin gene in a large Italian pedigree with familial amyloidotic polyneuropathy and demonstrate the presence of a Met30 mutation. The usefulness of the genetic analysis in the identification of presymptomatic persons and the diagnosis of individuals with partial symptoms is discussed. (+info)
Amyloid polyneuropathy in two German-American families: a new transthyretin variant (Val 107).
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We report studies on two German-American persons with systemic amyloidosis. Affected subjects presented with carpal tunnel syndrome in the sixth decade of life followed by peripheral neuropathy. DNA analysis of the transthyretin gene showed a new point mutation which is responsible for substitution of valine for isoleucine at position 107 of the transthyretin molecule. (+info)