Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Hereditary transthyretin amyloidosis (ATTRv) is endemic in northern Sweden (Västerbotten). The awareness of ATTRv amyloidosis is lower in Stockholm, a non-endemic region in Sweden. The aim of this study was to compare the possible differences in diagnostic delay, disease phenotypes, treatment and survival between a non-endemic and an endemic region in Sweden. ⋯ There was a diagnostic-, but no patient-delay in non-endemic Stockholm vs endemic Västerbotten. Despite a more severe neuropathic phenotype in Stockholm at the onset, the systemic affection over the course of disease and of survival seems not to be influenced by the diagnosis delay in Stockholm.
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Case Reports
A novel substitution of proline (P32L) destabilises β2-microglobulin inducing hereditary systemic amyloidosis.
β2-microglobulin amyloidosis was first described in the 1980s as a protein deposition disease associated with long-term haemodialysis. More recently, two inherited forms resulting from separate point mutations in the β2-microglobulin gene have been identified. In this report, we detail a novel β2M variant, P32L, caused by a unique dinucleotide mutation that is linked to systemic hereditary β2-microglobulin amyloidosis. ⋯ This work provides both clinical and experimental evidence supporting the critical role of P32 residue replacement in β2M amyloid fibrillogenesis.
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Lysozyme-derived (ALys) amyloidosis is a rare type of hereditary amyloidosis. Nine amyloidogenic variants and ∼30 affected families have been described worldwide. The most common manifestations are renal dysfunction, gastrointestinal tract symptoms, and sicca syndrome. ⋯ In summary, ALys amyloidosis is a very rare, but still heterogeneous disease that can manifest at an early age. Our newly identified lysozyme variant is associated with nephropathy and peripheral polyneuropathy. Further research is needed to understand its pathogenesis and to enable the development of new treatments.
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Hereditary transthyretin amyloidosis (ATTRv amyloidosis) results from pathogenic mutations in the transthyretin (TTR) gene. This analysis aimed to better understand ATTRv amyloidosis development in asymptomatic TTR gene carriers. ⋯ More than one-third of asymptomatic TTR gene carriers in THAOS developed ATTRv amyloidosis within a median 2 years of enrolment. Val30Met versus non-Val30Met patients had a lower transition rate. Given the importance of early treatment, these findings underscore the need for identification and careful monitoring of at-risk TTR gene carriers to enable prompt treatment.