Neurology-Genetics最新文献

{"title":"Shared Genetics of Migraine and Gastrointestinal Disorders Implicates Underlying Neurologic Mechanisms Yet Heterogeneous Etiologies.","authors":"Daniel I Chasman, Yanjun Guo, Andrew T Chan, Pamela M Rist, Kyle Staller","doi":"10.1212/NXG.0000000000200201","DOIUrl":"10.1212/NXG.0000000000200201","url":null,"abstract":"<p><strong>Background and objectives: </strong>Migraine is strongly comorbid with irritable bowel syndrome (IBS), one of several gastrointestinal (GI) conditions that are distinguished by symptomatic profiles that are partly overlapping. Potential shared mechanisms of migraine and the GI conditions were investigated by assessing shared genetics on a genome-wide basis.</p><p><strong>Methods: </strong>Analyses leveraged genome-wide summary statistics from large-scale genetic studies for migraine, including by aura status, IBS, peptic ulcer disease (PUD), gastrointestinal reflux (GERD), functional dyspepsia (FD), diverticular disease (DD), and the immune-related inflammatory bowel disease (IBD) or its constituents, ulcerative colitis (UC) and Crohn disease (CD). Genetic correlation was evaluated on a genome-wide basis and at independent local regions, including those related to therapeutic targeting of serotonin and the calcitonin gene-related peptide. Genetic correlation was assessed for enrichment at genes according to tissue specificity of gene expression. Potential causality between migraine and the GI conditions was assessed by Mendelian randomization.</p><p><strong>Results: </strong>Genetic correlation with migraine was strongly significant among the nonimmune GI disorders, maximally for IBS (rg [SE] = 0.37[0.04], <i>p</i> = 10^-21) and minimally for DD (0.18 (0.04), 7.5 × 10^-7), but null for IBD. There were distinct patterns of local genetic sharing with migraine across the GI conditions at 22 significant segments of the genome, 7 of which were novel for either migraine or GI or both. Enrichment analysis suggested involvement of the CNS in genetic overlap of GERD, IBS, and PUD with migraine. There was local genetic sharing with migraine at <i>CALCA/CALCB</i> (encoding calcitonin gene-related peptide [CGRP]) in an inverse sense for GERD and PUD, but with concordance and greater significance for DD, IBD, and UC. Mendelian randomization supported causal effects of PUD, GERD and particularly DD (OR[SE] = 1.90 (1.35-2.68, <i>p</i> = 2.2 × 10^-4) on migraine, but not of migraine on any GI condition.</p><p><strong>Discussion: </strong>Genetic sharing of migraine and non-immune-related GI disorders was extensive yet distinct across GI disorders that have overlapping symptoms, with enrichment signals that imply neurologic mechanisms. Causal effects of some GI conditions on migraine were supported. A concordant local correlation at <i>CALCA/CALCB</i> of migraine with both DD and the immune-related disorders suggests potential benefit to these conditions from repurposed migraine therapeutics targeting CGRP.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200201"},"PeriodicalIF":3.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Perspectives on Returning Genetic Research Results in Parkinson Disease.","authors":"Ai Huey Tan, Paula Saffie-Awad, Artur F Schumacher Schuh, Shen-Yang Lim, Harutyun Madoev, Azlina Ahmad-Annuar, J Solle, Claire E Wegel, Maria Leila Doquenia, Sumit Dey, Maria Teresa Perinan, Mary B Makarious, Brian Fiske, Huw R Morris, Alastair J Noyce, Roy N Alcalay, Kishore Raj Kumar, Christine Klein","doi":"10.1212/NXG.0000000000200213","DOIUrl":"https://doi.org/10.1212/NXG.0000000000200213","url":null,"abstract":"<p><strong>Background and objectives: </strong>In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable. However, research testing may not hold the same standards required from clinical diagnostic laboratories and hold significant psychosocial implications. The absence of universally recognized protocols complicates the establishment of appropriate guidelines.</p><p><strong>Methods: </strong>Aiming to develop recommendations on return of research results (RoR) practice within the Global Parkinson's Genetics Program (GP2), we conducted a global survey to gain insight on GP2 members' perceptions, practice, readiness, and needs surrounding RoR.</p><p><strong>Results: </strong>GP2 members (n = 191), representing 147 institutions and 60 countries across 6 continents, completed the survey. Access to clinical genetic testing services was significantly higher in high-income countries compared with low- and middle-income countries (96.6% vs 58.4%), where funding was predominantly covered by patients themselves. While 92.7% of the respondents agreed that genetic research results should be returned, levels of agreement were higher for clinically relevant results relating to pathogenic or likely pathogenic variants in genes known to cause PD or other neurodegenerative diseases. Less than 10% offered separate clinically accredited genetic testing before returning genetic research results. A total of 48.7% reported having a specific statement on RoR policy in their ethics consent form, while 53.9% collected data on participants' preferences on RoR prospectively. 24.1% had formal genetic counselling training. Notably, the comfort level in returning incidental genetic findings or returning results to unaffected individuals remains low.</p><p><strong>Discussion: </strong>Given the differences in resources and training for RoR, as well as ethical and regulatory considerations, tailored approaches are required to ensure equitable access to RoR. Several identified strategies to enhance RoR practices include improving informed consent processes, increasing capacity for genetic counselling including providing counselling toolkits for common genetic variants, broadening access to sustainable clinically accredited testing, building logistical infrastructure for RoR processes, and continuing public and health care education efforts on the important role of genetics in PD.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200213"},"PeriodicalIF":3.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nemaline Myopathy Type 6 Caused by Variants in the <i>KBTBD13</i> Gene: A Cross-Sectional Study of 24 Patients.","authors":"Esmee S B van Kleef, Karlijn Bouman, Joery P F Molenaar, Benno Küsters, Jan T Groothuis, Montse Olivé, Edoardo Malfatti, Erik-Jan Kamsteeg, Baziel G M Van Engelen, Coen A C Ottenheijm, Jonne Doorduin, Nicol C Voermans","doi":"10.1212/NXG.0000000000200214","DOIUrl":"10.1212/NXG.0000000000200214","url":null,"abstract":"<p><strong>Background and objectives: </strong>Nemaline myopathy type 6 (NEM6) is the most prevalent type of nemaline myopathy in the Netherlands. Because a detailed clinical characterization is not available yet, we here provide a detailed assessment of 24 patients.</p><p><strong>Methods: </strong>In this cross-sectional study, we performed a full clinical assessment (medical history and neurologic examination) in patients with NEM6. Patient demographics, causative variants in the <i>KBTBD13</i> gene, creatine kinase levels, and the results of previous muscle biopsies were collected. We evaluated experienced health-related quality of life, fatigue severity, prevalence of falls, balance control (Mini-Balance Evaluation Systems Test [Mini-BESTest]), functional motor score (Motor Function Measure [MFM]), and 6-minute walk distance. We used transcranial magnetic stimulation to assess muscle relaxation kinetics.</p><p><strong>Results: </strong>Twenty-four patients were included (19 women [19-76 years]; 5 men [25-57 years]). Key patient-reported symptoms since childhood were muscle weakness (n = 23; 96%), slowness of movements (n = 23; 96%), and difficulties with running (n = 20; 83%). Axial, proximal, and distal muscles showed mild weakness in most patients. Health-related quality of life was significantly lower, and there was a significantly increased fatigue severity compared with controls. Prospectively, in a period of 100 days, 8 patients (33%) fell at least 1 time, of whom 5 patients (21%) fell 2 times or more. The median total score on the Mini-BESTest was 24 (21.0-26.0 [interquartile range]) of 28 and the median total percentage on the MFM was 91% (83.5-95.3), both considered to be mildly abnormal. The 6-minute walk distance was below the lower limit of normal in 4 patients (17%). All patients with NEM6 showed a markedly reduced muscle relaxation rate with a median of 6.5 [4.9-8.1] s^-1 (lower limit of normal is 10.1 s^-1).</p><p><strong>Discussion: </strong>This cross-sectional study in patients with NEM6 shows a relatively mild clinical phenotype and mildly abnormal functional tests. However, patients report an important impact on the daily activities, which is illustrated by functional difficulties, reduced quality of life, increased fatigue severity, and increased prevalence of falls. This might be related to delayed muscle relaxation. This study provides a comprehensive overview of the clinical presentation and functional limitations in patients with NEM6.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200214"},"PeriodicalIF":3.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Muscle MRI to Monitor Disease Progression in Hypokalemic Period Paralysis.","authors":"Sonja Holm-Yildiz, Thomas Krag, Tina Dysgaard, Britt Stævnsbo Pedersen, Nanna Witting, Louise Sloth Kodal, Linda Kannuberg, Jonas Jalili Pedersen, Zhe Lyu, Morten Müller Aagaard, John Vissing","doi":"10.1212/NXG.0000000000200211","DOIUrl":"10.1212/NXG.0000000000200211","url":null,"abstract":"<p><strong>Background and objectives: </strong>Primary hypokalemic periodic paralysis (HypoPP) is a muscle channelopathy that can cause periodic paralysis and permanent weakness. Currently, little is known about how progressive this myopathy is. Natural history data for HypoPP can potentially answer the question of progressiveness and form the basis for outcome measures to be used in follow-up and emerging treatment trials. We aimed to describe the natural history of HypoPP and assess whether quantitative fat imaging is a valuable biomarker to monitor disease progression.</p><p><strong>Methods: </strong>In this prospective follow-up study, we examined disease progression using Dixon MRI to monitor changes in fat replacement of the muscle and stationary dynamometry to monitor changes in muscle strength.</p><p><strong>Results: </strong>We included 37 persons (mean age 43 years, range 18-79 years) with HypoPP-causing variants in <i>CACNA1S</i>. Three participants were asymptomatic carriers, 22 had periodic paralysis, 3 had permanent weakness, and 9 had periodic paralysis in combination with permanent weakness. The median follow-up time was 20 months (range 12-25). We found that fat fraction increased in 10 of 21 examined muscles. An increase in the composite fat fraction of at least 1 muscle group was found in all symptomatic phenotypes. By contrast, we found no significant change in muscle strength.</p><p><strong>Discussion: </strong>The results from this follow-up study support the use of quantitative muscle MRI to monitor subclinical disease progression in HypoPP in patients with and without attacks of paralysis.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200211"},"PeriodicalIF":3.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult Neuropsychiatric Manifestation of Hartnup Disease With a Novel <i>SLCA6A19</i> Variant: A Case Report.","authors":"Tobias Bachmann, Helene Faust, Rami Abou Jamra, Christina Pott, Michael Kluge, Jost-Julian Rumpf, Florian Then Bergh, Skadi Beblo","doi":"10.1212/NXG.0000000000200195","DOIUrl":"10.1212/NXG.0000000000200195","url":null,"abstract":"<p><strong>Objectives: </strong>In adults, inborn metabolic diseases are often missed in routine diagnostic settings due to a low level of suspicion.</p><p><strong>Methods: </strong>A patient in their twenties was admitted for an apparent acute exacerbation of anxiety disorder. Medical treatment was unsuccessful, and presumed catatonic psychosis was treated by electroconvulsive treatment. The patient was referred to neurology with reduced level of consciousness, mutism with no targeted movements, obvious anxiety and tetraspasticity, eczema, and reduced body weight.</p><p><strong>Results: </strong>EEG was normal; repeat brain MRI showed progressive atrophy and leukoencephalopathy. Autoimmune encephalitis was assumed and treated with plasma exchange, high-dose glucocorticoids, and intravenous immunoglobulin. Repeated CSF analyses remained normal. Metabolic workup showed hyperaminociduria, low neutral amino acids, and undetectable tryptophane. Whole-exome sequencing and segregation analysis revealed compound heterozygous, pathogenic and a novel, likely pathogenic variant in the <i>SLC6A19</i> gene: c.718C>T, p.(Arg240*) and c.170G>A, p.(Arg57His). Diagnosing Hartnup disease, high-protein diet, and niacin supplementation led to rapid considerable improvement. At 4 months, plasma amino acids were normal; communication and behavior were age-adequate; and spasticity had almost resolved, but polyneuropathy was unchanged.</p><p><strong>Discussion: </strong>Metabolic workup and whole-exome sequencing are recommended in rapidly progressive neuropsychiatric disease, especially with additional neurologic signs and when standard treatment fails.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200195"},"PeriodicalIF":3.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapidly Progressing and Early-Onset Forms of Amyotrophic Lateral Sclerosis Caused by a Novel <i>SOD1</i> Variant in a Lithuanian Family.","authors":"Domantas Valančius, Birutė Burnytė, Raminta Masaitienė, Aušra Morkūnienė, Aušra Klimašauskienė","doi":"10.1212/NXG.0000000000200217","DOIUrl":"10.1212/NXG.0000000000200217","url":null,"abstract":"<p><strong>Objectives: </strong>To describe a novel familial variant of superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS) in a Lithuanian family, highlighting its variable progression and implications for treatment inclusion criteria.</p><p><strong>Methods: </strong>This study presents the clinical and genetic findings of a family with the novel <i>SOD1</i> variant, including one member diagnosed with early-onset ALS (onset <40 years) and one with a particularly rapidly progressing course of ALS.</p><p><strong>Results: </strong>The <i>SOD1</i> variant NM_000454.5:c.446T>C, NP_000445.1:p.(Val149Ala) was identified in affected family members and 4 asymptomatic members aged 32-56 years. We present detailed disease course of the affected family members obtained during follow-up. Clinically, this variant is associated with variable disease progression, with the time from symptom onset to death ranging from 5 to 77 months.</p><p><strong>Discussion: </strong>The novel <i>SOD1</i> variant p.Val149Ala in this Lithuanian family causes ALS of variable onset and course, including a case of early-onset ALS and one case of rapidly progressing ALS, necessitating recognition by the scientific community and development of tailored therapeutic approaches.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200217"},"PeriodicalIF":3.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Complex <i>SMN</i> Hybrids Detected in a Cohort of 31 Patients With Spinal Muscular Atrophy.","authors":"","doi":"10.1212/NXG.0000000000200212","DOIUrl":"https://doi.org/10.1212/NXG.0000000000200212","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1212/NXG.0000000000200175.].</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200212"},"PeriodicalIF":3.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>TTN</i>-Related Muscular Dystrophies, LGMD, and TMD, in an Estonian Family Caused by the Finnish Founder Variant.","authors":"Katrin Õunap, Tiia Reimand, Eve Õiglane-Shlik, Sanna Puusepp, Laura Mihkla, Sander Pajusalu, Marco Savarese, Bjarne Udd","doi":"10.1212/NXG.0000000000200199","DOIUrl":"https://doi.org/10.1212/NXG.0000000000200199","url":null,"abstract":"<p><strong>Background and objectives: </strong>Tibial muscular dystrophy (TMD) is an autosomal dominant, slowly progressive late-onset distal myopathy. TMD was first described in 1991 by Udd et al. in Finnish patients, who were later found to harbor a heterozygous unique 11-bp insertion/deletion in the last exon of the <i>TTN</i> gene-the Finnish founder variant (FINmaj). In homozygous state or compound heterozygosity with a truncating variant, the FINmaj causes early-onset recessive titin-related limb-girdle muscular dystrophy type 10 (LGMD R10). So far, the FINmaj variant has not been detected outside the Finnish population.</p><p><strong>Methods: </strong>We describe an Estonian family presenting both early-onset LGMD R10 and late-onset TMD. The index patient underwent trio exome sequencing (ES), muscle biopsy, and RNA sequencing. The detected variants were validated by Sanger sequencing. Muscle MRI was performed in all affected individuals.</p><p><strong>Results: </strong>Trio ES revealed 2 heterozygous variants in the <i>TTN</i> gene: (NM_001267550.2):c.107780_107790delinsTGAAAGAAAAA, p.(Glu35927_Trp35930delinsValLysGluLys) (FINmaj variant, paternally inherited) and (NM_001267550.2):c.64672+2dup (maternally inherited) in trans in the proband. Familial segregation analysis revealed the same biallelic variants in the younger affected sister and heterozygous FINmaj in the father. We characterized the effect of the splice variant by RNA sequencing, proving that it causes an intronic retention resulting in a premature stop codon. Muscle histology of the proband showed myopathic changes. Muscle MRI of both individuals with LGMD R10 showed early degenerative changes in tibialis anterior and in hypotrophy of distal hamstrings. Muscle MRI of the father with TMD, at the age of 38 years, showed early minimal fatty degeneration in the peroneus longus and right tibialis anterior muscles.</p><p><strong>Discussion: </strong>For the first time, we have detected the FINmaj variant in the Estonian population. We report an Estonian family without any known Finnish ancestry for many generations, with 2 siblings harboring FINmaj in a compound with a splice site variant and their father with heterozygous FINmaj. It is currently not known whether the FINmaj is originally Estonian or Finnish ancestry. Further population studies in Estonia to establish the frequency of FINmaj in the population are ongoing and will solve the quest.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200199"},"PeriodicalIF":3.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosing Late-Onset Tay-Sachs Through Next Generation Sequencing and Functional Enzyme Testing: From Genes to Enzymes.","authors":"Ajay R Tupil, Warwick Rivlin, Pamela A Mccombe, Robert D Henderson, Jonathan Rodgers, Lata Vadlamudi","doi":"10.1212/NXG.0000000000200205","DOIUrl":"https://doi.org/10.1212/NXG.0000000000200205","url":null,"abstract":"<p><p>Tay-Sachs disease is a neurodegenerative disorder characterized by progressive neurologic impairment due to pathogenic variants in the <i>HEXA</i> gene that codes for the alpha subunit of β-hexosaminidase. We report 2 cases of adult-onset progressive weakness, ataxia, and neuropsychiatric symptoms in a 30-year-old man and 37-year-old woman. Both patients had compound heterozygosity in the <i>HEXA</i> gene with 4 distinct variants. The first patient had subsequent confirmatory functional enzyme testing displaying reduced hexosaminidase concentration, and the second patient had functional enzyme testing before genetic testing, exemplifying alternative avenues for the diagnosis of late-onset Tay-Sachs (LOTS) disease.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200205"},"PeriodicalIF":3.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Approach to Longitudinal Neurologic Care of Adults With X-Linked Adrenoleukodystrophy and Adrenomyeloneuropathy.","authors":"Alexandra B Kornbluh, Aaron Baldwin, Ali Fatemi, Adeline Vanderver, Laura A Adang, Keith Van Haren, Jacinda Sampson, Florian S Eichler, Reza Sadjadi, Marc Engelen, Jennifer L Orthmann-Murphy","doi":"10.1212/NXG.0000000000200192","DOIUrl":"10.1212/NXG.0000000000200192","url":null,"abstract":"<p><p>Although X-linked adrenoleukodystrophy (ALD) has historically been considered a childhood disease managed by pediatric neurologists, it is one of the most common leukodystrophies diagnosed in adulthood. An increase in both male and female adults reaching diagnosis due to familial cases identified by state newborn screening panels and more widespread use of genetic testing results in a large cohort of presymptomatic or early symptomatic adults. This population is in urgent need of standardized assessments and follow-up care. Adults with ALD/adrenomyeloneuropathy (AMN) may be diagnosed in a variety of ways, including after another family member is identified via genetic testing or newborn screening, presenting for symptomatic evaluation, or following diagnosis with primary adrenal insufficiency. Significant provider, patient, and systems-based barriers prevent adult patients with ALD/AMN from receiving appropriate care, including lack of awareness of the importance of longitudinal neurologic management. Confirmation of and education about the diagnosis should be coordinated in conjunction with a genetic counselor. Routine surveillance for adrenal insufficiency and onset of cerebral ALD (CALD) in men should be performed systematically to avoid preventable morbidity and mortality. While women with ALD do not usually develop cerebral demyelination or adrenal insufficiency, they remain at risk for myeloneuropathy and are no longer considered \"carriers.\" After diagnosis, patients should be connected to the robust support networks, foundations, and research organizations available for ALD/AMN. Core principles of neurologic symptom management parallel those for patients with other etiologies of progressive spastic paraplegia. Appropriate patient candidates for hematopoietic stem cell transplant (HSCT) and other investigational disease-modifying strategies require early identification to achieve optimal outcomes. All patients with ALD/AMN, regardless of sex, age, or symptom severity, benefit from a multidisciplinary approach to longitudinal care spearheaded by the neurologist. This review proposes key strategies for diagnostic confirmation, laboratory and imaging surveillance, approach to symptom management, and guidance for identification of appropriate candidates for HSCT and investigational treatments.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 5","pages":"e200192"},"PeriodicalIF":3.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}