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The American Journal of Cardiology Jun 2024
Topics: Humans; Prognosis; Prealbumin; Protein Folding; Amyloid Neuropathies, Familial; Mutation
PubMed: 38657853
DOI: 10.1016/j.amjcard.2024.04.028 -
European Journal of Nuclear Medicine... Jul 2024
Letter to the editor concerning "Cardiac [99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?".
Topics: Humans; Amyloid Neuropathies, Familial; Organotechnetium Compounds; Radionuclide Imaging; Bone and Bones; Biological Transport; Radiopharmaceuticals; Follow-Up Studies; Myocardium; Diphosphonates; Biomarkers; Heart
PubMed: 38653815
DOI: 10.1007/s00259-024-06724-8 -
Clinical Nuclear Medicine Jul 2024A 57-year-old woman who had persistent symptoms of transthyretin cardiac amyloidosis underwent 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy. The 99m Tc-PYP planar and...
A 57-year-old woman who had persistent symptoms of transthyretin cardiac amyloidosis underwent 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy. The 99m Tc-PYP planar and SPECT/CT fusion image showed diffuse myocardial uptake and multiple fractures of the sternum and ribs. These fractures interfered with semiquantitative scores of 99m Tc-PYP uptake, leading to false positive in 99m Tc-PYP imaging.
Topics: Humans; Female; Middle Aged; Technetium Tc 99m Pyrophosphate; Single Photon Emission Computed Tomography Computed Tomography; Amyloid Neuropathies, Familial; Amyloidosis; Cardiomyopathies; Fractures, Bone
PubMed: 38651782
DOI: 10.1097/RLU.0000000000005230 -
Revue Neurologique Apr 2024We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of...
OBJECTIVE
We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg.
METHODS
Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance.
RESULTS
Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients.
CONCLUSION
In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.
PubMed: 38643028
DOI: 10.1016/j.neurol.2024.02.393 -
European Journal of Heart Failure Apr 2024
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Cardiomyopathies; Amyloid Neuropathies, Familial
PubMed: 38623722
DOI: 10.1002/ejhf.3245 -
Neurological Sciences : Official... Apr 2024Hereditary transthyretin (ATTRv, v for variant) amyloidosis with polyneuropathy is a rare disease caused by mutations in the transthyretin gene. In ATTRv amyloidosis,...
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/m; 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.
PubMed: 38622453
DOI: 10.1007/s10072-024-07494-9 -
CMAJ : Canadian Medical Association... Apr 2024
Topics: Humans; Carpal Tunnel Syndrome; Amyloid Neuropathies, Familial
PubMed: 38621774
DOI: 10.1503/cmaj.230671-f -
European Journal of Ophthalmology Apr 2024Genetic mutations or inflammatory, degenerative, or neoplastic conditions can trigger amyloidosis. Hereditary gelsolin amyloidosis is a genetic disorder primarily marked...
INTRODUCTION
Genetic mutations or inflammatory, degenerative, or neoplastic conditions can trigger amyloidosis. Hereditary gelsolin amyloidosis is a genetic disorder primarily marked by amyloid fibrils composed of misfolded gelsolin fragments.
CASE REPORT
We present three sisters with AGel amyloidosis, illustrating its clinical diversity. Patient 1, a 51-year-old, had bilateral ptosis, ocular discomfort, and dry eye syndrome due to cranial nerve involvement. Patient 2, a 53-year-old, experienced progressive bilateral visual impairment. Patient 3, a 50-year-old, exhibited right eye ectropion. Genetic analysis, with the identical mutation, heterozygous c.640G > A (p.Asp214Asn) mutation, confirmed AGel amyloidosis diagnoses, with common findings including lattice corneal amyloidosis, reduced corneal sensitivity, and recurrent corneal erosions. Neurological manifestations included ataxia and peripheral neuropathy, with skin abnormalities observed in patient 1. Ocular involvement severity and distribution varied among patients.
DISCUSSION
Common ocular and neurological manifestations validated AGel amyloidosis diagnoses, reinforcing its hereditary basis. Neurological symptoms highlighted the disorder's impact on various organ systems, while skin abnormalities contributed to ocular discomfort. Variable ocular involvement emphasized the disorder's heterogeneity. These patients emphasize hereditary gelsolin amyloidosis's clinical diversity and suggest potential environmental influences on disease expression. Genetic confirmation and confocal microscopy findings reaffirm the genetic basis while raising questions about assessing systemic disease severity, necessitating further investigation in larger cohorts. Ophthalmologists' specialized care is crucial for managing ocular symptoms, given the absence of a universal cure.
PubMed: 38619860
DOI: 10.1177/11206721241247586 -
Medicina Clinica Jun 2024Transthyretin-related amyloidosis (ATTRv) is a progressive multisystem disorder, predominantly involving the peripheral nerve system (PNS) and heart. Quantification of...
INTRODUCTION
Transthyretin-related amyloidosis (ATTRv) is a progressive multisystem disorder, predominantly involving the peripheral nerve system (PNS) and heart. Quantification of small fiber damage may help guide treatment decisions, as amyloid deposits frequently affect those fibers early in disease course. Corneal confocal microscopy (CCM) is a promising method to monitor patients with ATTRv, due to similarities between corneal nerves and PNS, as the cornea is innervated by Aδ and C fibers.
METHODS
We compared CCM measures from ATTRv patients to a group of healthy individuals, matched by age and gender. We then investigated the correlations between small fiber tests (SFT): CCM, LDI-Flare and CDT, COMPASS-31 and disability scales (RODS and ONLS) in patients.
RESULTS
Of 20 patients (6 with V30M), mean age 50.3±15.3Y, 7 female (35%), six (30%) had polyneuropathy and 10 (50%) carpal tunnel syndrome. CDT was abnormal in 9 and LDI-flare in 6 patients. CCM was abnormal in 19 tested patients and significantly reduced when compared to controls (CNFL: 6.31±0.31 vs. 15.21±1.02mm/mm, p<0.001). Mean COMPASS-31-scores were 22.27±22.84; RODS and ONLS were 38.15±12.33 and 2.05±2.3, with no significant differences between sub-group scores. Disease duration was significantly correlated with ONLS (0.43, p=0.05) and RODS (0.46, p=0.03). There were no significant correlations between measures of disability and SFT.
CONCLUSIONS
In a diverse cohort of ATTRv patients, CCM was the most frequent abnormal measurement. CCM can be a useful test to triage patients in the early disease stages and with few or equivocal symptoms.
Topics: Humans; Female; Male; Amyloid Neuropathies, Familial; Middle Aged; Adult; Aged; Cornea; Microscopy, Confocal; Case-Control Studies; Carpal Tunnel Syndrome; Nerve Fibers
PubMed: 38616431
DOI: 10.1016/j.medcli.2024.02.012 -
Medicina Clinica Jun 2024Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, progressive, and debilitating genetic disorder characterized by the deposition of abnormal... (Review)
Review
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.
Topics: Humans; Early Diagnosis; Amyloid Neuropathies, Familial; Prealbumin
PubMed: 38614903
DOI: 10.1016/j.medcli.2024.02.013