Early Onset Research Articles

Latent class analysis of communication methods and devices among Japanese patients with amyotrophic lateral sclerosis: a cross-sectional survey

ABSTRACT Augmentative and alternative communication (AAC) is used to support individuals with communication impairments, such as those with amyotrophic lateral sclerosis (ALS). The selection of AAC for patients with ALS involves a variety of factors, sometimes leading to the utilization of multiple AAC methods. This study aimed to survey patients with ALS in Japan, focusing on objectives: to describe the actual state of AAC usage among these patients and to investigate potential classifications in their choice of communication methods, along with identifying influential latent factors. Data from 102 patients with ALS were analysed using descriptive statistics and latent class analysis. A latent class analysis revealed four distinct classifications: class I, replacing unaid communication with AAC (n = 46, 45.1%); class II, with minimal AAC use (n = 24, 23.5%); class III, centred around no-tech/low-tech AAC (n = 17, 16.7%); and class IV combining unaid communication with various AACs (n = 15, 14.7%). These classifications were influenced by age at diagnosis, TPPV use, gastrostomy use, and the Revised ALS Functional Rating Scale. The characteristics of each class revealed a correlation between increased medical needs, such as bulbar palsy, motor and respiratory function decline, and the necessity for AAC. Notably, patients diagnosed at an older age and those with severe bulbar palsy, like those seen in bulbar-onset ALS, require early communication support due to early onset of communication impairments. Additionally, introducing AAC in the early stages of ALS suggests that learning diverse communication methods can contribute to the maintenance of communication.

Patterns of alcohol consumption in Mexico and mortality from alcohol consumption related diseases: an epidemiological state-clustered study

ABSTRACT Objective The present study aims to describe the patterns of alcohol consumption in Mexico by state, emphasizing the age at onset of alcohol consumption and the epidemiologic magnitude of deaths due to the selected causes related to these medical conditions. Methods This epidemiological study has an observational, descriptive, and retrospective design. A total of 73,088 deaths occurred in Mexico due to alcoholic cardiomyopathy, alcohol-induced pancreatitis, and alcoholic liver disease between 2016 and 2020; the annual rate was 11.3 in 2016 and 12.3 in 2020, showing an increase in the studied period. Results The early onset of alcohol drinking was reported by one of every four responders. Individuals with binge drinking patterns reported an onset of < 18 years of age in 37.8%. At the state level, in Mexico, the early onset of alcohol consumption and binge drinking are directly correlated with age at death due to alcoholic cardiomyopathy, alcohol-induced pancreatitis, and alcoholic liver disease, with average age at death of 55.5 years. Discussion Multilevel, cross-national, and multidisciplinary measures are urgently needed because mortality due to alcohol consumption is a preventable problem. Still, many more issues of social and health-related nature can also be prevented by approaching the alcohol consumption patterns.

Climate-driven decline in water level causes earlier onset of hypoxia in a subtropical reservoir

Hypoxia, especially in the bottom water, is occurring in deep and stratified reservoirs worldwide, threatening aquatic biodiversity, ecosystem functions and services. However, little is known about the timing of onset and ending of hypoxia, especially in subtropical reservoirs. Based on five-year (from April 2015 to January 2020) sampling of a subtropical monomictic deep reservoir (Tingxi Reservoir) in southeast China, we found the evidence of about 40 days earlier onset of hypolimnion hypoxia during low water level periods in dry years compared to wetter high water level years. We explored the effects of stratification and mixing conditions on hypoxia, cyanobacterial biomass, and nutrient dynamics; and revealed the physical and biochemical conditions that drove hypoxia. The results indicated that 1) The decline in water level increased the intensity of thermal stratification, resulting in 40 days earlier onset of hypolimnion hypoxia in dry years than in wet years; 2) The decline in water level expanded the extent of hypoxia by promoting nutrient accumulation and phytoplankton biomass growth; 3) Warmer climate and less precipitation (drought) significantly promoted the risk of hypoxic expansion and endogenous phosphorus release in subtropical reservoirs. We suggest that more attention needs to be paid to the early onset of hypoxia and its consequences on water quality in subtropical stratified reservoirs during low water level periods in a changing climate.

Association of Increased Homocysteine Level with Impaired Folate Metabolism and Vitamins B Deficiency in Early Onset of Multiple Sclerosis

Association of Increased Homocysteine Level with Impaired Folate Metabolism and Vitamins B Deficiency in Early Onset of Multiple Sclerosis

Updated reference values for BMD and lean mass measured by DXA in Thai children.

This study established normative references for total body less head (TBLH) BMD, lumbar spine (L1-L4) BMD, and both total and appendicular lean mass (LM) in Thai children and adolescents (aged 5-18years) using DXA. This work expands upon 2014 normative data for Thai children, which included L2-L4 BMD, total body BMD (head included), and total LM. We reanalyzed total body and lumbar spine DXA scans (Lunar Prodigy Pro, GE Healthcare; enCORE version 7.53) from 174 boys and 193 girls, using upgraded software (enCORE version 17SP2) for TBLH BMD, L1-L4 BMD, and LM analysis. The "enhanced" mode was applied for TBLH BMD and LM. Adjustments for total and appendicular LM were made relative to squared height (m2) to account for body size variability. Normative data stratified by sex and Tanner stage were generated for TBLH BMD, L1-L4 BMD, and LM indices. Weight and Tanner stage significantly determined BMD and LM. Adolescent girls exhibited higher LSBMD values due to earlier pubertal onset. Boys showed higher LM indices with more rapid gains during growth spurts. This study provides updated normative reference values for BMD (TBLH and L1-L4) and LM (total and appendicular) in Thai children and adolescents, measured via DXA. These references will enhance the assessment of low bone mass and LM deficits in Thai pediatric populations, particularly in those with chronic illnesses.

Effect of multi-directional compression on microstructure and mechanical properties of Tip/WE43 composite

Titanium (Ti) particle-reinforced Mg-4Y–2Nd-1Gd-0.5Zr (WE43) magnesium (Mg) matrix composite (Tip/WE43) was prepared via vacuum hot-pressing sintering. The multi-directional compression (MDC) treatment significantly enhanced the material's strength, and the MDC 6 wt% Tip/WE43 composite exhibits exceptional mechanical properties, with a yield strength (YS) of 255 MPa, ultimate tensile strength (UTS) of 316 MPa, and elongation (EL) of 8.9 %. The presence of Ti particles within the composite hinders the basal slip of the Mg matrix during plastic deformation, facilitating the early onset of tensile twinning. The Ti particles contribute to grain refinement, inhibit slip deformation, and promote the occurrence of additional twins within the grains. The second phase, Mg41Nd5, is distributed along the powder boundaries, with dislocation tangles observed within the grains. Twin boundary strengthening is identified as the primary factor for the increased YS in the MDC 6Tip/WE43 composite. Additionally, the MDC 6Tip/WE43 composite demonstrates superior thermal conductivity compared to the MDC WE43 alloy, which is attributed to its less pronounced basal texture.

B - 125 Atypical Alzheimer’s Disease in a Highly Educated Individual: a Case Study

Abstract Objective Early onset of atypical Alzheimer’s disease (ad) can be challenging to identify, especially in highly educated individuals. Protein deposits in neural areas other than the medial temporal lobe can be associated with a heterogeneous neurocognitive pattern. We present a case that highlights the value of biomarker studies in these individuals. Method A 67-year-old, right-handed female with 18 years of education presented with inefficient word retrieval and mental set loss, which emerged approximately two to three years prior. Symptoms worsened in the context of gabapentin use status post lung cancer resection without return to baseline with steady progression. Remaining medical history includes a 1.4 cm right parietal falcine meningioma, hyperlipidemia, and depression. Results In the context of high average premorbid functioning, challenges included complex executive functioning, subtle visuospatial deficits, and encoding and recall inefficiencies. Naming was low average. Neuroimaging revealed mild parietal and dorsal frontal atrophy, potentially age-appropriate, with no significant hippocampal atrophy. Conclusions The present case highlights the possibility of atypical protein deposits and neurocognitive pattern in a highly educated individual with the potential of an early onset ad process. The value of biomarkers and neuropsychological nuances will be of increasing relevance in the context of emerging amyloid therapies.

Trends in Norwegian adolescents’ substance use between 2014 and 2022: socioeconomic and gender differences

BackgroundSubstance use is a global health concern and early onset among adolescents increases health risks. We explore national overall trends in prevalence and trends in socioeconomic inequalities in past year alcohol intoxication, cannabis use, and use of other illicit drugs among Norwegian adolescents (ages ∼ 15–19 years of age) between 2014 and 2022.MethodThe present study builds on data from a nationwide repeated cross-sectional survey collected in 2014–2016 (T1), 2017–2019 (T2), 2021 (T3) and 2022 (T4). In total 415,560 adolescents (50.3% girls) completed the questionnaire during the study period. Trends in socioeconomic inequalities were assessed using the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII).ResultsWhile the prevalence of alcohol intoxication remained fairly stable, the prevalence of cannabis and other illicit drug use increased between 2014 and 2022 among upper secondary school boys (13.3–17.6%, and 2.0–5.2%, respectively) and girls (8.8–12.8%, and 1.1–2.7%, respectively). Similar trends were observed among 10th-grade adolescents. Boys were more likely than girls to use cannabis or other illicit drugs, but the gender gap in cannabis use narrowed during the study period. Among upper secondary girls, use of cannabis and other illicit drugs was higher among those from less affluent backgrounds, with absolute and relative inequalities in cannabis use increasing between 2014 and 2022. Small inequalities in cannabis use and decreasing relative inequalities in the use of other illicit drug were observed among upper secondary boys.ConclusionsThe increasing use of cannabis and other illicit drugs among Norwegian adolescents is concerning. Future studies should explore the underlying causes of this rise and explore the complex factors influencing adolescent substance use behaviours. A comprehensive understanding of these factors is essential for developing targeted and effective interventions.

A - 130 Effectiveness of Beta-Amyloid Immunotherapy and Monoclonal Antibodies in Patients with Early Onset Alzheimer’s between the Ages of 45–60 Years

Abstract Objective This comprehensive systematic review examines various therapeutic approaches for Alzheimer’s Disease (ad), with a specific emphasis on immunotherapy targeting beta-amyloid and tau pathology. Data Selection Data were sourced from peer-reviewed journals, databases (e.g., PubMed, PsychInfo, Scielo, Google Scholar), and relevant conference proceedings from inception to present. Search terms included variations of “Alzheimer’s disease,” “clinical trials,” “monoclonal antibodies,” “beta amyloid,” “immunotherapy”. Selection criteria emphasized relevance to ad therapy, randomized controlled trials, and clinical outcomes. A total of 24 studies from 2013 to 2023 were reviewed, meeting robust study design, sample size, and therapeutic relevance were chosen. Data extraction followed standardized guidelines for abstracting key information, including study design, participant characteristics, interventions, and outcome measures. Data Synthesis The review synthesized recent studies on Alzheimer’s disease (ad) therapy, particularly monoclonal antibodies targeting amyloid beta oligomers. Notable studies such as Avgerinos et al. (2021) and Bateman et al. (2022), showcased significant cognitive decline reductions in ad patients. Positive outcomes were also observed with gantenerumab, lecanemab, and donanemab. Additionally, alternative approaches such as Zanthoxylum caribaeum extract and herbal extracts were explored. The synthesis underscored the complexity of ad treatment and the necessity for continued multidisciplinary research. Conclusions This systematic review provides valuable insights into ad therapeutics, guiding future research directions and informing clinical practice to better meet the needs of ad patients and their caregivers. Despite significant advancements, challenges persist in developing effective ad therapies, underscoring the ongoing need for research, particularly in immunotherapy and natural compounds, to address the multifaceted nature of the disease and enhance patient outcomes.

Role of Gastric Aspirate Polymorphs in Diagnosis of Early Onset Neonatal Sepsis

Role of Gastric Aspirate Polymorphs in Diagnosis of Early Onset Neonatal Sepsis

Clinical spectrum and outcome of children with deficiency of adenosine deaminase 2 (DADA2): multicentric experience from India.

Deficiency of adenosine deaminase-2 (DADA2) is a monogenic disorder closely resembling polyarteritis nodosa (PAN) and can present to physicians across various specialties. Through this case series, we aim to describe the clinical spectrum and outcome of Indian children with DADA2. We aimed to study the clinical spectrum and outcome of Indian children with DADA-2. The deidentified data from all participating centres were entered in an excel sheet, and the coordinating centre (All India Institute of Medical Sciences, New Delhi) screened the data for accuracy and completeness. We enrolled 16 children (11 females) in the study; the mean (SD) age at the time of onset of symptoms for males and females was 46.2 (47) and 73.6 (50.4) months, respectively. The most common clinical feature in this cohort was fever and rash in 80% of patients. More than half of children n, (%) [8, (53%)] had a CNS stroke. The other clinical features were hypertension [5(33%)], anaemia [3 (20%)] and arthralgia/arthritis in 4 (26%). These children were managed with various immunomodulators: steroids [13, (86%)], anti-TNF agents [(12, (80%)], cyclophosphamide [2 (13%)] and mycophenolate mofetil [3 (20%)]. The median (IQR) duration of follow-up for this cohort was 17 (10, 29) months. Fourteen children achieved remission and none had recurrent strokes after the initiation of anti-TNF drugs. DADA-2 closely resembles PAN; early age of onset and CNS stroke are striking differentiating features from classic PAN. Most children respond well to anti-TNF agents without serious adverse events during short-term follow-up.

Investigating the associations between early labour onset symptoms and self-diagnosed labour onset in a cohort study of primiparas

ObjectiveThe early recognition of possible labour onset symptoms may be pivotal to identifying the beginning of early labour and are usually recognised by the birthing women themselves. The present study illustrates the interrelationship among five labour-onset symptoms and explores the association of these labour-onset symptoms with the self-diagnosed labour onset of primiparas. MethodsA prospective cohort study on a sample of 69 primigravida in Giessen, Germany, expecting spontaneous onset of labour at term. The participants filled in a diary from ≥37 + 0 weeks gestation until self-diagnosed labour onset. Descriptive, bivariate and inferential analysis explored association of labour onset symptoms with self-diagnosed labour onset while accounting for maternal and newborn characteristics. ResultsSelf-diagnosed labour onset was positively associated with all symptoms and clinical characteristics, apart from irregular pain and maternal weight and age. Moreover, regular pain was negatively correlated with irregular pain; having regular pain increased the odds of self-diagnosed labour onset substantially (OR: 10.18, 95 % CI: 2.39–66.27), followed by gastrointestinal symptoms (OR: 2.07, 95 % CI: 0.40–13.10) and emotional symptoms (OR: 2.05, 95% CI: 0.30–13.98). ConclusionBeing the initiator of intrapartum care without any birth experience, primiparas are prone to experiencing dissatisfaction in care and may enter professional care too late or too early. The present study showed that regular pain may signify primiparas to self-diagnose labour onset within 24 h and indicate early labour symptoms that may be relevant for a self-diagnosed labour onset.

An algorithm for drug-resistant epilepsy in Danish national registers.

Patients with drug-resistant epilepsy (DRE) have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life. Identification of persons with DRE in administrative data can allow for effective large-scale research, and we therefore aimed to construct an algorithm for identification of DRE in Danish nation-wide health registers. We used a previously generated sample of 525 persons with medical record-validated incident epilepsy between 2010-2019, of which 80 (15%) fulfilled International League Against Epilepsy (ILAE) criteria of DRE at the time of the latest contact - this cohort was considered the gold standard. We linked information in the validated cohort to Danish national health registers and constructed register-based algorithms for identification of DRE-cases. The accuracy of each algorithm was validated against the medical record-validated gold standard. We applied the best performing algorithm according to test accuracy (F1 score) to a large cohort with incident epilepsy identified in the Danish National Patient Registry between 1995 and 2013 and performed descriptive and logistic regression analyses to characterize the cohort with DRE as identified by the algorithm. The best performing algorithm in terms of F1 score was defined as 'fillings of prescriptions for ≥ 3 distinct antiseizure medications (ASMs) within 3 years or acute hospital visit with epilepsy/convulsions following fillings of prescriptions for two distinct ASMs' (sensitivity 0.59, specificity 0.93, positive predictive value 0.59, negative predictive value 0.92, area under the receiver operating characteristic curve 0.77, and F1 score 0.595). Applying the algorithm to a register-based cohort of 83,682 individuals with incident epilepsy yielded 8,650 cases (10.3 %) with DRE. In multivariable logistic regression analysis, early onset of epilepsy, focal or generalized epilepsy, somatic co-morbidity, and substance abuse, were independently associated with risk of being classified with DRE. We developed an algorithm for the identification of DRE in Danish national registers, which can be applied for a variety of research questions. We identified early onset of epilepsy, focal or generalized epilepsy, somatic co-morbidity, and substance abuse as risk factors for DRE.

Impaired Skeletal Development by Disruption of Presenilin-1 in Pigs and Generation of Novel Pig Models for Alzheimer's Disease.

Presenilin 1 (PSEN1) is one of the genes linked to the prevalence of early onset Alzheimer's disease. In mice, inactivation of Psen1 leads to developmental defects, including vertebral malformation and neural development. However, little is known about the role of PSEN1 during the development in other species. To investigate the role of PSEN1 in vertebral development and the pathogenic mechanism of neurodegeneration using a pig model. CRISPR/Cas9 system was used to generate pigs with different mutations flanking exon 9 of PSEN1, including those with a deleted exon 9 (Δexon9). Vertebral malformations in PSEN1 mutant pigs were examined by X-ray, micro-CT and micro-MRI. Neuronal cells from the brains of PSEN1 mutant pigs were analyzed by immunoflourescence, followed by image analysis including morphometric evaluation via image J and 3D reconstruction. Pigs with a PSEN1 null mutation (Δexon9-12) died shortly after birth and had significant axial skeletal defects, whereas pigs carrying at least one Δexon9 allele developed normally and remained healthy. Effects of the null mutation on abnormal skeletal development were also observed in fetuses at day 40 of gestation. Abnormal distribution of astrocytes and microglia in the brain was detected in two PSEN1 mutant pigs examined compared to age-matched control pigs. The founder pigs were bred to establish and age PSEN1ΔE9/+ pigs to study their relevance to clinical Alzheimer's diseases. PSEN1 has a critical role for normal vertebral development and PSEN1 mutant pigs serves as novel resources to study Alzheimer's disease.

Clinical manifestations, treatment and prognosis of juvenile idiopathic arthritis with pulmonary involvement in China: a single centre study.

In recent years, the distinct clinical presentations and elevated mortality rates of various subtypes of juvenile idiopathic arthritis (JIA) with pulmonary involvement have garnered significant attention. This study aimed to elucidate the clinical characteristics of pulmonary involvement in patients with JIA to improve clinicians' knowledge. This single-centre retrospective study analysed the baseline data, treatment options, follow-up of sixty patients of JIA with pulmonary involvement in China. Patients with interstitial lung disease (ILD) were further classified in accordance with the 2013 American Thoracic Society/European Respiratory Society International multidisciplinary consensus on idiopathic interstitial pneumonia. Sixty patients (5.03%) with JIA were complicated with pulmonary involvement. The highest subtype was systemic JIA (sJIA, 63.3%), followed by rheumatoid factor (RF)-positive polyarthritis (pJIA, 25.0%). The incidence of macrophage activation syndrome (MAS) was 21.6%. The most common diagnosis was ILD (90%). Respiratory symptoms/signs were initially experienced by 61.7% of the patients, and respiratory support was required by 21.7%. High-resolution CT classification of sJIA revealed non-specific interstitial pneumonia (NSIP) and organising pneumonia. High-resolution CT classification of pJIA was NSIP and usually interstitial pneumonia (UIP). Patients were treated with NSAIDs, along with glucocorticoids, DMARDs, and biological agents. The survival rates after 1 and 5 years were approximately 93.3% and 90.0%, respectively. Patients with JIA with pulmonary involvement present with early onset, high mortality rate. JIA patients should undergo physical examination thoroughly and high-resolution CT scans, lung function tests for evaluating and monitoring the occurrence and development of pulmonary involvement in early stages to improve prognosis.

Stratigraphic overview of the Neogene Transylvanian Basin, Romania

Although the Transylvanian Basin is often referred as part of the Miocene Pannonian Basin System, we point out important tectonic and sedimentary differences reflected in the stratigraphy. The Neogene of the Transylvanian Basin can be split into two tectonic megasequences: Lower Miocene and Middle to Upper Miocene. The Early Miocene onset of the back arc extension in the Pannonian Basin was not observed in the Transylvanian Basin, where shallow to deep marine sediments were deposited in a flexural basin. Diverse types of facies developed in the continental (e.g., Sânmihai) and marine (e.g., Coruş, Chechiş, Hida) Lower Miocene formations. Although these are poorly constrained to the standard biostratigraphy, recent 87 Sr- 86 Sr data support their limited correlation with the Burdigalian. The Middle Miocene extension in the Transylvanian Basin is very weak compared to that the Pannonian Basin. As the high-resolution Middle Miocene regional biostratigraphy of the Badenian and Sarmatian was calibrated by magnetostratigraphy and radiometric dating of the volcanic tuffs up to the Serravallian/Tortonian boundary, the influence of the regional tectonics on the basin's evolution and stratigraphy can be better understood. The regional tectonics produced a progressive basin isolation starting with the late part of the Middle Miocene. The uplift of the Carpathians isolated the basin at the beginning of the Pannonian and initiated the fan delta, lacustrine, and fluvial sedimentation. The basin was rapidly uplifted and eroded, while post-extensional subsidence was still ongoing in the Pannonian Basin. Endemic fossil assemblages allow only regional-scale correlations for this interval. The uppermost part of the stratigraphic record is represented by the volcano-sedimentary formations generated by the late evolution of the Eastern Carpathians. The sedimentation and subsidence pattern of the Transylvanian Basin reflect the effect of retreating subduction zone in the Eastern Carpathians.

Rationally designed catalytic nanoplatform for enhanced chemoimmunotherapy via deploying endogenous plus exogenous copper and remodeling tumor microenvironment

Chemodynamic therapy represents a novel tumor therapeutic modality via triggering catalytic reactions in tumors to yield highly toxic reactive oxygen species (ROS). Nevertheless, low efficiency catalytic ability, potential systemic toxicity and inefficient tumor targeting, have hindered the efficacy of chemodynamic therapy. Herein, a rationally designed catalytic nanoplatform, composed of folate acid conjugated liposomes loaded with copper peroxide (CP) and chloroquine (CQ; a clinical drug) (denoted as CC@LPF), could power maximal tumor cytotoxicity, mechanistically via maneuvering endogenous and exogenous copper for a highly efficient catalytic reaction. Despite a massive autophagosome accumulation elicited by CP-powered autophagic initiation and CQ-induced autolysosomal blockage, the robust ROS, but not aberrant autophagy, underlies the synergistic tumor inhibition. Otherwise, this combined mode also elicits an early onset, above all, long-term high-level existence of immunogenic cell death markers, associated with ROS and aberrant autophagy -triggered endoplasmic reticulum stress. Besides, CC@LPF, with tumor targeting capability and selective tumor cytotoxicity, could elicit intratumor dendritic cells (mainly attributed to CQ) and tumor infiltrating CD8+ T cells, upon combining with PD-L1 therapeutic antibody, further induce significant anti-tumor effect. Collectively, the rationally designed nanoplatform, CC@LPF, could enhance tumor chemoimmunotherapy via deploying endogenous plus exogenous copper and remodeling tumor microenvironment.Graphical abstract

Family reflections: research gives back childhood: a family's experience with very early onset inflammatory bowel disease.

Family reflections: research gives back childhood: a family's experience with very early onset inflammatory bowel disease.

The Gly103Arg variant in hereditary transthyretin amyloidosis.

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited systematic disease primarily affecting the peripheral and autonomic nervous system, heart, eyes and kidney. Over 140 variants have been identified worldwide, with the Gly103Arg variant reported exclusively in China. This variant is characterized by early onset eye manifestations, making accurate and timely diagnosis difficult. Therefore, we conducted a case study and literature review to investigate the clinical characteristics of the Gly103Arg variant in hereditary transthyretin amyloidosis. We identified three patients and an asymptomatic carrier in a four-generation family by sequencing the TTR gene. The proband underwent a lumbar puncture, electromyography, abdominal fat biopsy, among other tests. Case reports of Gly103Arg variant were retrieved through a literature search for an analysis of clinical characteristics. The study included clinical data of 44 patients. Our literature review collected data on 41 patients and the present report supplied 3 patients with the Gly103Arg variant. The mean age at onset was 39.1 ± 4.27 years (range 30-47 years) with a female ratio of 52.3%. All cases were reported in China, predominantly in southern regions, especially Yunan and Guizhou Provinces. The initial manifestation was blurred vision, except for one case presenting with numbness in the upper extremities. All of them had vitreous opacity; 17 cases had peripheral neuropathy,6 cases had autonomic neuropathy, and 3 cases had cardiopathy. No disease-related deaths have been reported to date. The Gly103Arg variant is unique to the Chinese population, frequently occurring in southern China. The main clinical manifestations are blurred vision, vitreous opacity, and neuropathy, with cardiopathy being rare. ATTRv should be considered if a patient diagnosed with CIDP does not respond to related therapy. Abdominal fat biopsy is a convenient and accurate diagnostic method.

Clinical and genetic features of CMT2T in Italian patients confirm the importance of MME pathogenic variants in idiopathic, late‐onset axonal neuropathies

AbstractBackground and AimsSince 2016, biallelic mutations in the membrane metalloendopeptidase (MME) gene have been associated with late‐onset recessive CMT2 (CMT2T). More recently, heterozygous mutations have also been identified in familial and sporadic patients with late‐onset axonal neuropathy, ranging from subclinical to severe. This indicates that the heterozygous MME variants may not be fully penetrant, or alternatively, that they may be a potential risk factor for neuropathy. Here, we describe the clinical, neurophysiological, and genetic findings of 32 CM2T Italian patients.MethodsThe patients were recruited from four different Italian referral centers. Following a comprehensive battery of neurological, electrophysiological, and laboratory examinations, the patients' DNA was subjected to sequencing in order to identify any variants in the gene. Bioinformatic and modeling analyses were performed to evaluate the identified variants' effects.ResultsWe observe a relatively mild axonal sensory‐motor neuropathy with a greater impairment of the lower extremities. Biallelic and monoallelic patients exhibit comparable disease severity, with an earlier onset observed in those with biallelic variants. When considering a subgroup with more than 10 years of disease, it becomes evident that biallelic patients exhibit a more severe form of neuropathy. This suggests that they are more prone to quick progression.InterpretationCM2T has been definitively defined as a late‐onset neuropathy, with a typical onset in the fifth to sixth decades of life and a more rapidly progressing worsening for biallelic patients. CMT2T can be included in the neuropathies of the elderly, particularly if MME variants heterozygous patients are included.