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Background: Hereditary transthyretin amyloidosis (ATTRv; v for variant) with polyneuropathy is a rare, progressive, and fatal autosomal dominant disorder. Therapies such as liver transplantation and TTR stabilizations have limitations. Patisiran is a small interfering RNA (siRNA), offering potential as a genetic-level therapy for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). However, evidence on patisiran's efficacy and safety for ATTRv-PN remains limited. Objectives: This study aimed to further clarify patisiran's efficacy and safety for ATTRv-PN by meta-analysis. Design: Systematic review and meta-analysis. Methods: After literature searches in PubMed, Ovid MEDLINE, Embase, JBI EBP, Cochrane, and ClinicalTrials.gov databases on 7 June 2024, 11 studies with 503 patients were included and clinical data were extracted. Results: Results showed an 88% (95% confidence interval (CI): 81%-94%) pooled responsiveness rate. The standardized mean difference of modified Neuropathy Impairment Score plus 7 nerve tests (mNIS + 7) scores was -0.18 (95% CI: -0.32 to -0.03, p-value 0.018) and Norfolk Quality of Life-Diabetic Neuropathy was -0.21 (95% CI: -0.35 to -0.08, p-value 0.002). In total, 413 adverse events (AEs) (84.8%), 158 serious AEs (32.4%), and 37 deaths (7.6%) were recorded. Most of AEs were mild to moderate. No deaths were attributed to patisiran. However, there is no statistically significant improvement in Neuropathy Impairment Scores. Conclusion: In conclusion, patisiran was effective and safe for patients with ATTRv-PN. More large-scale clinical trials and long-term studies are necessary to further validate patisiran's efficacy and safety. Trial registration: PROSPERO registration ID: CRD42023428838.

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Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant, adult-onset disease that stems from point mutations in the TTR gene encoding the protein transthyretin. The disease is progressive and life-threatening and is associated with amyloid deposits in multiple organs including the heart, kidney, skin, eyes, nervous system, and gastrointestinal tract. Genotypic and phenotypic heterogeneity is a characteristic hallmark of hereditary transthyretin amyloidosis. Herein, we present a rare variant of hATTR cardiomyopathy secondary to Ser97Tyr mutation, having been documented only in a handful of families previously. This case serves as a valuable opportunity to elucidate the clinico-pathogenesis of this disease, highlight the aggressive nature of this genetic mutation (c.290C>A; p.Ser97Tyr), and document the response to the latest advances in treatment currently available.

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BACKGROUND: Previously, T2-relaxation time (T2app) and proton spin density (ρ) detected nerve injury in a small group of ATTRv amyloidosis. Here, we aim to quantify peripheral nerve impairment in a large cohort of symptomatic and asymptomatic ATTRv amyloidosis and correlate T2-relaxometry markers with clinical parameters and nerve conduction studies (NCS). METHODS: Eighty participants with pathologic variants of the transthyretin gene (TTRv) and 40 controls prospectively underwent magnetic resonance neurography. T2-relaxometry was performed, allowing to calculate tibial ρ, T2app and cross-sectional-area (CSA). Detailed clinical examinations and NCS of tibial and peroneal nerves were performed. RESULTS: Forty participants were classified as asymptomatic TTRv-carriers, 40 as symptomatic patients with polyneuropathy. ρ, T2app and CSA were significantly higher in symptomatic ATTRv amyloidosis (484.2 ± 14.8 a.u.; 70.6 ± 1.8 ms; 25.7 ± 0.9 mm2) versus TTRv-carriers (413.1 ± 9.4 a.u., p < 0.0001; 62.3 ± 1.3 ms, p = 0.0002; 19.0 ± 0.8 mm2, p < 0.0001) and versus controls (362.6 ± 7.5 a.u., p < 0.0001; 59.5 ± 1.0 ms, p < 0.0001; 15.4 ± 0.5 mm2, p < 0.0001). Only ρ and CSA differentiated TTRv-carriers from controls. ρ and CSA correlated with NCS in TTRv-carriers, while T2app correlated with NCS in symptomatic ATTRv amyloidosis. Both ρ and T2app correlated with clinical score. CONCLUSION: ρ and CSA can detect early nerve injury and correlate with electrophysiology in asymptomatic TTRv-carriers. T2app increases only in symptomatic ATTRv amyloidosis in whom it correlates with clinical scores and electrophysiology. Our results suggest that T2-relaxometry can provide biomarkers for disease- and therapy-monitoring in the future.

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This article has been co-authored by a patient living with hereditary transthyretin (ATTRv) amyloidosis and a neurologist. This rare, progressive disease is associated with impairment of multiple organ systems, including the nerves, heart, and the gastrointestinal tract, forcing patients to live with and adapt to a range of debilitating symptoms. Here, the patient and physician discuss how the symptoms of ATTRv amyloidosis profoundly impact day to day life, the difficulties with identifying the disease, and how this effects the diagnosis experience. In recent years, significant advancements have been made in the treatment and management of ATTRv amyloidosis. However, the authors highlight the urgency of increasing awareness of the disease among the wider medical community, as well as in patients who notice the symptoms, to ensure that earlier diagnosis and appropriate treatment are achieved.

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Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score). Blood samples were collected from 16 patients diagnosed with ATTRv amyloidosis and a verified TTR variant and from 26 healthy controls. ATTRv patients were stratified by clinical phenotype (neurologic vs. mixed), genotype (V30M vs. non-V30M), and disease severity. We found significantly higher levels of serum GDF-15 in ATTRv patients compared with controls. Mean serum Umod levels were significantly lower in patients with ATTRv than controls. A positive correlation was found between serum Umod and estimated glomerular filtration rate (eGFR), while an inverse correlation was found with cystatin C levels. Conversely, GDF-15 showed a negative correlation with eGFR, and a direct correlation with cystatin C levels. No correlation was demonstrated between GDF-15 or Umod levels and traditional cardiac biomarkers. The results identify alteration of serum levels of GDF-15 and Umod in ATTRv amyloidosis.

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Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant, life-threatening genetic disorder caused by a single-nucleotide variant in the transthyretin gene. This mutation leads to the misfolding and deposition of amyloid in various body organs. Both mutant and wild-type transthyretin contribute to the resulting polyneuropathy and cardiomyopathy, leading to significant sensorimotor disturbances and severe cardiac conditions such as heart failure and arrhythmias, thereby impacting quality of life. Despite several treatments, including orthotopic liver transplantation and transthyretin tetramer stabilizers, their limitations persisted until the introduction of RNA interference (RNAi). RNAi, a means to regulate mRNA stability and translation of targeted genes, has brought about significant changes in treatment strategies for ATTR with the introduction of patisiran in 2018. This study reviews patisiran, vutrisiran, inotersen, and eplontersen, developed for the treatment of ATTR. It provides an overview of the clinical trial outcomes, focusing mainly on quality of life, adverse reactions, and the future of RNAi-based therapies.

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BACKGROUND: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN. METHODS: Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed. RESULTS: Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability. CONCLUSIONS: Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.

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Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the TTR gene. The His90Asn mutation has been previously reported in several reports, but its pathogenetic role is still debated. We report two sporadic cases of adult women with a heterozygous His90Asn mutation in TTR gene and neurological involvement extensively investigated. A typical Congo red-positive pathologic deposition of amyloid fibrils in the salivary glands was documented in one subject. Patients were successfully treated with patisiran with a good clinical outcome. These data support a pathogenetic role of His90Asn mutation in hATTR, and suggest early treatment in symptomatic carriers of His90Asn mutation.

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Objectives: Evidence on the activity of patisiran therapy in specific subgroups of patients with hereditary transthyretin amyloidosis variant (ATTRv) is still scarce. This prospective real-world study was designed to provide the first in-depth clinical data on the effectiveness of patisiran in patients with ATTRv reporting the p.Ile88Leu variant, the most widespread variant in the Emilia-Romagna regional area, which has been less represented in previous clinical trials. Patients and methods: This prospective study evaluated all the patients with genetically proven ATTRv (p.Ile88Leu) and polyneuropathy treated with patisiran in the Emilia-Romagna referral centers for ATTRv (Institute of Neurological Sciences in Bologna and Division of Neurology in Rimini) from March 2021 to April 2023. All subjects underwent clinical and neurological evaluations at baseline and after 9-12 months of treatment. Results: A total of 22 patients were included in the study; the median age was 73 years (IQR: 9), the age at diagnosis was 72 years (IQR: 10), and the disease duration was 1.6 years (IQR: 2.3). We observed stability of all considered neurological and cardiological parameters at 9-12 months after the beginning of patisiran treatment. Conclusion: Our findings support the clinical data regarding the effectiveness of patisiran in stabilizing the disease course and extend this activity to the subset of patients with the p.Ile88Leu variant.

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BACKGROUND: Recent evidence suggests that both serum neurofilament light chain (sNfL) levels and small fiber related diagnostic variables may be valuable disease biomarkers of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). Our study aimed to explore the relations between sNfL and small fiber related skin biopsy and quantitative sensory testing (QST) parameters in a cohort of ATTRv-PN patients and pre-symptomatic carriers. METHODS: We retrospectively analyzed data from 13 ATTRv patients and 21 pre-symptomatic carriers who underwent sNfL dosage, skin biopsy, and QST, and analyzed correlations between sNFL, intraepidermal nerve fiber density (IENFD), and cold (CDT) and warm detection thresholds (WDT). RESULTS: Both sNfL and small fiber related parameters significantly differed between carriers and patients (sNfL: p < 0.0001; IENFD: p = 0.0008; CDT, WDT: < 0.0001). sNFL levels were normal in all carriers, altered in 85% of patients, negatively correlated with distal IENFD (r = -0.47, p = 0.005), and significantly correlated with CDT (r = -0.68; p < 0.0001) and WDT (r = 0.57; p < 0.0001). CONCLUSIONS: Our study showed that sNfL reliably discriminates symptomatic ATTRv-PN patients from pre-symptomatic carriers, and found significant relations between sNfL, skin biopsy, and QST small fiber related parameters, suggesting that sNfL might be a valuable biomarker of peripheral nerve involvement in ATTRv-PN and a supportive criterion for symptomatic disease transition.

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Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, progressive, and debilitating genetic disorder characterized by the deposition of abnormal transthyretin (TTR) protein aggregates in various tissues, leading to organ dysfunction. Early diagnosis of ATTRv amyloidosis is critical for starting timely interventions and improving patient outcomes. This review explores the concepts of "how early is enough" and "how early is possible" in the context of diagnosing ATTRv amyloidosis, highlighting the challenges and opportunities for early recognition.

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BACKGROUND: Hereditary transthyretin (ATTRv, v for variant) amyloidosis with polyneuropathy is a rare disease caused by mutations in the transthyretin gene. In ATTRv amyloidosis, multisystem extracellular deposits of amyloid cause tissue and organ dysfunction. Patisiran is a small interfering RNA molecule drug that reduces circulating levels of mutant and wild-type TTR proteins. Prior to its regulatory approval, patisiran was available in Italy through a compassionate use programme (CUP). The aim of this study was to analyse the long-term outcomes of patients who entered into the CUP. METHODS: This was a multicentre, observational, retrospective study of patients with ATTRv amyloidosis treated with patisiran. The analysis included change from baseline to 12, 24, 36 and 48 months in familial amyloid polyneuropathy (FAP) stage, polyneuropathy disability (PND) class, neuropathy impairment score (NIS), modified body mass index (mBMI), Compound Autonomic Dysfunction Test (CADT), Karnofsky Performance Status (KPS) scale and Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire. Safety data were also analysed. RESULTS: Forty patients from 11 Italian centres were enrolled: 23 in FAP 1 (6 in PND 1 and 17 in PND 2) and 17 in FAP 2 (8 in PND 3a and 9 in PND 3b) stage. In this population, the mean NIS at baseline was 71.4 (± 27.8); mBMI, 917.1 (± 207) kg/m2; KPS, 67.1 (± 14.0); Norfolk QoL-DN, 62.2 (± 25.2); and CADT, 13.2 (± 3.3). Statistical analysis showed few significant differences from baseline denoting disease stability. No new safety signals emerged. CONCLUSIONS: Patisiran largely stabilised disease in patients with ATTRv amyloidosis.

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Hereditary transthyretin (TTR) amyloidosis (ATTRv amyloidosis) is autosomal dominant and caused by mutation of TTR gene. Heterozygous ATTR Tyr114Cys (p.Tyr134Cys) amyloidosis is a lethal disease with a life expectancy of about 10 years after onset of the disease. However, the molecular pathogenesis of ATTR Tyr114Cys amyloidosis is still largely unknown. In this study, we took advantage of disease-specific induced pluripotent stem (iPS) cells and generated & characterized the heterozygous ATTR Tyr114Cys amyloidosis-specific iPS cells (Y114C iPS cells), to determine whether Y114C iPS cells could be useful for elucidating the pathogenesis of ATTR Tyr114Cys amyloidosis. We successfully differentiated heterozygous Y114C iPS cells into hepatocyte like cells (HLCs) mainly producing TTR protein. On day 27 after differentiation, the expression of hepatocyte maker albumin was detected, and TTR expression was significantly increased in HLCs differentiated from Y114C iPS cells. LC-MS/MS analysis showed that both WT TTR & ATTR Y114C protein were indeed expressed in the HLCs differentiated from Y114C iPS cells. Notably, the number of detected peptides derived from ATTR Y114C protein was lower than that of WT TTR protein, indeed indicating the clinical phenotype of ATTR Tyr114Cys amyloidosis. Taken together, we first reported the heterozygous Y114C iPS cells generated from patient with ATTR Tyr114Cys amyloidosis, and suggested that Y114C iPS cells could be a potential pathological tool, which may contribute to elucidating the molecular pathogenesis of heterozygous ATTR Tyr114Cys amyloidosis.

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BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM. METHODS AND RESULTS: We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P=0.028), whereas the control group showed no significant change (4.079 to 3.915, P=0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, P=0.007). CONCLUSIONS: The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

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INTRODUCTION: There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. METHODS: Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. RESULTS: Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire-diabetic neuropathy]. CONCLUSION: QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN.

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INTRODUCTION/AIMS: In the early stage, hereditary transthyretin (ATTRv) amyloidosis predominantly affects small nerve fibers, resulting in autonomic dysfunction and impaired sensation of pain and temperature. Evaluation of small fiber neuropathy (SFN) is therefore important for early diagnosis and treatment of ATTRv amyloidosis. Herein, we aimed to investigate the accuracy of a quick and non-invasive commercial sudomotor function test (SFT) for the assessment of SFN in ATTRv amyloidosis. METHODS: We performed the SFT in 39 Japanese adults with ATTRv amyloidosis, and we analyzed the correlations between electrochemical skin conductance (ESC) values obtained via the SFT and the parameters of other neuropathy assessment methods. RESULTS: ESC in the feet demonstrated significant, moderate correlations with intraepidermal nerve fiber density (IENFD) results (Spearman's rank correlation coefficient [rs ], 0.58; p < .002) and other neuropathy assessment methods including the sensory nerve action potential amplitude in the nerve conduction studies (rs , 0.52; p < .001), the Neuropathy Impairment Score (rs , -0.45; p < .01), the heat-pain detection threshold (rs , -0.62; p < .0001), and the autonomic section of the Kumamoto ATTRv clinical score (rs , -0.53; p < .0001). DISCUSSION: In this study, we found that ESC values in the feet via the SFT demonstrated significant, moderate correlations with IENFD and other SFN assessment methods in patients with ATTRv amyloidosis, suggesting that the SFT appears to be an appropriate method for assessment of SFN in this disease.

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BACKGROUND: Hereditary transthyretin (ATTRv) amyloidosis is a heterogeneous, progressive, multisystemic disease with a life-threatening course if left untreated. Given the current availability of effective therapies, close follow-up of presymptomatic TTR mutation carriers is essential to recognize disease onset at the earliest sign. In addition to routine techniques, in recent years several novel tools have been proposed, although a consensus on their use has not been reached yet. In this paper, we aimed to evaluate possible markers of neuropathic disease onset intended to discriminate clinically asymptomatic carriers from early symptomatic patients, thus allowing timely treatment initiation. METHODS: Thirty-eight presymptomatic carriers were enrolled. Clinical and electrophysiological findings at first evaluation and follow-up were collected. All carriers underwent an extensive clinical and instrumental evaluation according to the standard clinical practice. One or more non-routine investigations, whose use in this field is not yet validated (henceforth "unconventional"), were additionally assessed in a subgroup of individuals. RESULTS: Based on the exclusive use of routine investigations, it was possible to define disease onset in 4/38 carriers during the follow-up. Employing additionally one or more "unconventional" tests, abnormal findings, indicative of a possible "conversion" to symptomatic disease, were detected in further 12 cases. More than half of our study cohort showed findings suggestive of small nerve fiber (SF) involvement at either invasive or non-invasive tests. CONCLUSIONS: A close, multidisciplinary monitoring of presymptomatic TTR mutation carriers is fundamental, and diagnostic workup should include both routine and "unconventional" tests. Assessment of SF involvement is important also in non-endemic countries.

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The first small interfering RNA (siRNA) therapeutic received approval for hereditary transthyretin (ATTRv) amyloidosis, and the patients' lifespan extension by specific inhibition of hepatic synthesis of transthyretin (TTR) is expected. However, ocular amyloidosis in these patients has been a crucial issue. This study aims to evaluate the efficacy and safety of intravitreal TTR siRNA conjugate injection into rabbit eyes. Rabbit (r) TTR siRNA is a screened TTR siRNA conjugate from 53 candidates. The intraocular pressure (IOP) immediately after injection was high despite the 65.9 % decrease of aqueous humor TTR protein levels in the rTTR siRNA group compared with those in the Control siRNA group 2 weeks after the 50 µL siRNA injection. The IOP spike was milder after the 30 µL siRNA injection, and aqueous humor TTR levels decreased by ∼50 % in the rTTR siRNA group, which is consistent with the mRNA levels in the retina. The parameters of dark-adapted, light-adapted, and light-adapted 30 Hz electroretinogram and the thickness of each retinal layer in histological analysis demonstrated no significant differences between the groups. In conclusion, we developed TTR siRNA conjugates for rabbit eyes, and the results indicate that intravitreal TTR siRNA conjugate injection could be a therapeutic option for ocular amyloidosis caused by ATTRv amyloidosis.

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Gastrointestinal manifestations are common across all hereditary transthyretin amyloidosis (ATTRv) genotypes. However, they are poorly specific, and their recognition as part of ATTRv is difficult, resulting in misdiagnosis with more common conditions. Moreover, delays in diagnosis occur because of fragmented knowledge, a shortage of centers of excellence and specialists dedicated to ATTRv management, and the scarce involvement of gastroenterologists in multidisciplinary teams. A group of Italian gastroenterologists with experience in the management of ATTRv took part in a project aimed at assessing the awareness of ATTRv among the community of Italian gastroenterologists through an online survey and providing education about practical aspects of ATTRv management. Survey results reported low participation, and very few patients with ATTRv were cared for by gastroenterologists. This highlights the need for greater attention to rare diseases in gastroenterology and emphasizes increasing awareness of ATTRv and diagnostic suspicion. Based on the experts' recommendations, a diagnosis of ATTRv should be suspected when at least one of the 'red flags' is detected. Subsequently, it is suggested to promptly ask for genetic testing and exclude a serum and urinary monoclonal protein, even before the detection of amyloid in biopsy samples, particularly in non-endemic areas.

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BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a rare genetic disease that negatively affects patients' quality of life through the involvement of various organs and tissues. Despite a large amount of research on medical and psychosocial interventions, the impact of occupational therapy (OT) on patients with ATTRv is not well understood. OBJECTIVE: The aim of this study was to develop an OT programme to improve the daily functioning and quality of life of patients with ATTRv. METHODS: Fourteen patients with ATTRv were interviewed. Together they developed short- and medium-term occupational goals. Patients received the OT intervention for six months. Outcomes were measured using scores for activities of daily living and psychological well-being. RESULTS: The study found that OT can have a positive impact as a complementary intervention to medical and other psychosocial treatments. Of the 14 patients, 12 maintained the same scores in activities of daily living. Two deteriorated and eight improved their psychological scores. CONCLUSION: This study highlights the need for further research in this area and the importance of OT in the management of patients with ATTRv. Early intervention is of paramount importance and further research is needed to evaluate the long-term effects of OT interventions in patients with ATTRv.

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