Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Observational Study
Pharyngo-laryngeal involvement in systemic amyloidosis with cardiac involvement: a prospective observational study.
Background: Systemic amyloidosis with cardiac involvement (CA) is a severe disease caused by the aggregation of misfolded proteins infiltrating organs and tissues and leading to their dysfunction. No study has yet focused on potential pharyngo-laryngeal impairments associated to CA. Our objective was to define its prevalence and describe pharyngo-laryngeal involvement patterns in a population with CA (light chain: AL, wild-type transthyretin: ATTRwt, variant transthyretin: ATTRv). ⋯ VESS showed functional swallowing impairment in only 4 patients without any macroscopic organic lesion. Dysphonia was reported in 36% of the patients (44% and 47% in AL and ATTRv sub-groups, respectively) of whom 40% had functional or organic laryngeal abnormality (14% of vocal fold mobility dysfunction and 26% of abnormal mucosa) without any macroscopic-specific lesions of amyloid infiltration in these patients. Conclusions: This prospective study suggests, for the first time, that amyloid associated with CA could infiltrate the various anatomical structures of the pharyngo-larynx, responsible for functional impairment and potential nutritional depletion and poor quality of life.
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Objective: To characterize the changing spectrum of amyloidosis classes, as well as patient demographics, at a major US referral centre. Patients and methods: A retrospective analysis was conducted of all referrals to the Amyloidosis Centre at Boston University and Boston Medical Centre over the last 3 decades. Results: A total of 3987 new patients with amyloidosis were evaluated between 1990 and 2018 with the average number of new cases per year increasing 2.5-fold during this period. ⋯ Conclusion: Amyloid diseases are more widely recognized and classes of amyloidosis, including ATTRwt and ATTRV122I, once considered rare are now increasingly diagnosed. These data likely reflect a national trend of increased amyloidosis awareness facilitated by accessible diagnostic approaches, emerging treatments, and coordinated educational initiatives. ClinicalTrials.gov identifier: NCT00898235.
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Observational Study
Prevalence of TTR variants detected by whole-exome sequencing in hypertrophic cardiomyopathy.
Background: A proportion of patients with hypertrophic cardiomyopathy (HCM) have a diagnosis of cardiac amyloidosis. Hereditary transthyretin amyloid cardiomyopathy (ATTRv-CM) is caused by mutations in the TTR gene. Our aim was to study the prevalence of potentially amyloidogenic TTR variants in a whole-exome sequencing (WES) study of a large HCM cohort. ⋯ V142I) variant. Conclusions: Pathogenic TTR variants are rare in carefully assessed HCM patients and may occur in double heterozygosity with pathogenic sarcomere variants. The lack of evidence for an amyloidosis phenotype in all but one TTR variant carrier illustrates the importance of complete clinical evaluation of HCM patients that harbour pathogenic TTR variants.
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Background: Renal involvement is one of the most common complications of light-chain (AL) amyloidosis. For evaluating renal prognosis, two staging systems for renal involvement have been proposed, one in 2014 and one in 2017. However, the two staging systems have not yet been compared and widely used in clinic. ⋯ A significant difference in terms of requiring dialysis was seen only between stage 3 (24 h proteinuria to eGFR ≥100 mg/ml/min/1.73 m2) and the two other stages (p = 0.008). Conclusions: The prognostic value of the criteria based on eGFR and 24-hour proteinuria for predicting dialysis has been confirmed. These results might benefit guiding clinical treatment.
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Hereditary transthyretin amyloidosis is an autosomal dominant genetic disorder caused by missense mutations in the TTR gene resulting in amyloid formation of the transthyretin protein. Depending on the system affection, the manifestations may be different and high heterogeneity in the penetrance is observed. An endemic region in Bulgaria exists where the TTR mutation Glu89Gln is found with high frequency. ⋯ The common ancestry of the carriers was demonstrated using additional data for their genealogies and microsatellite data from a control group of non-affected individuals. The results show that the mutation Glu89Gln is linked to one haplotype, called "hypothetical founder haplotype" which was compared to published haplotype data from other European patients and no similarity was found. Further population genetics studies of carriers of the Glu89Gln mutation from other endemic regions are required in order to clarify the geographical distribution of the mutation.