Neurology-Genetics最新文献

{"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":"TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons.","authors":"Mohammad-Reza Ghovanloo, Philip R Effraim, Sidharth Tyagi, Alecia M Aldrich, Xiaoyang Cheng, Jun-Hui Yuan, Betsy R Schulman, Deborah S Jacobs, Sulayman D Dib-Hajj, Stephen G Waxman","doi":"10.1212/NXG.0000000000200206","DOIUrl":"10.1212/NXG.0000000000200206","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite extensive efforts, the mechanisms underlying pain after axonal injury remain incompletely understood. Pain following corneal refractive surgery offers a valuable human model for investigating trigeminal axonal injury because laser-assisted in situ keratomileusis (LASIK) severs axons of trigeminal ganglion neurons innervating the cornea. While the majority of patients are pain-free shortly after surgery, a minority endure persistent postoperative ocular pain. Through genomic analysis of patients experiencing persistent postoperative ocular pain, we identified rare variants in genes encoding ion channels and receptors, including TRPM8, which codes for the menthol-sensitive and cold-sensing transient receptor potential cation channel.</p><p><strong>Methods: </strong>We conducted a profiling of 2 TRPM8 mutant variants, D665N and V915M, which were identified in patients suffering from persistent pain after LASIK surgery. We used patch-clamp and multielectrode array (MEA) recordings to investigate the biophysical and pharmacologic properties of mutant vs wild-type (WT) channels.</p><p><strong>Results: </strong>Patch-clamp analysis shows that these mutations shift the activation curves of TRPM8 in a hyperpolarized direction, with this effect being significantly different between WT and D665N channels. In addition, both mutations significantly increase channel sensitivity to the canonical ligand, menthol. MEA recordings from transfected rat trigeminal ganglion neurons indicate that expression of D665N and V915M mutant channels increases spontaneous activity compared with WT channels. Consistent with patch-clamp results, neuronal activity in MEA recordings was increased on exposure to menthol.</p><p><strong>Discussion: </strong>Collectively, our findings suggest that proexcitatory mutations of TRPM8, in the context of axonal injury within the cornea, can produce trigeminal ganglion neuron hyperexcitability that contributes to persistent postoperative ocular pain. In addition to providing additional evidence for a role of TRPM8 in human pain, our results suggest that inhibitors of this channel merit future study.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200206"},"PeriodicalIF":3.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649382","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":"Progressive Apraxia of Speech as a Manifestation of Spinocerebellar Ataxia 2: Case Report.","authors":"Audrey M Blazek, Gabriela Meade, Lauren M Jackson, Ralitza Gavrilova, Julie Stierwalt, Jennifer M Martinez-Thompson, Joseph R Duffy, Heather Clark, Mary M Machulda, Jennifer L Whitwell, Keith A Josephs, Rene L Utianski, Hugo Botha","doi":"10.1212/NXG.0000000000200202","DOIUrl":"10.1212/NXG.0000000000200202","url":null,"abstract":"<p><strong>Objectives: </strong>To describe a case of spinocerebellar ataxia presenting with progressive apraxia of speech (AOS).</p><p><strong>Methods: </strong>A 54-year-old man with progressive speech changes was seen clinically and referred to our observational research program on degenerative speech and language disorders. He underwent detailed speech-language and neurologic assessments and multimodal neuroimaging studies. Three board-certified speech-language pathologists, blinded to other study data, reached a consensus speech diagnosis.</p><p><strong>Results: </strong>The patient reported 2 years of progressive speech changes against a background of mild imbalance. Speech alternating and sequential motion rates were regular but moderately slow. He segmented syllables, most prominently during repetition of multisyllabic words, and had decreased prosodic variation in connected speech. He was diagnosed with prosodic-predominant primary progressive AOS. He had mild extremity ataxia and difficulty with tandem gait on neurologic examination. MRI showed marked pontine-cerebellar atrophy. FDG-PET showed premotor area and posterior fossa hypometabolism. Genetic testing revealed cytosine-adenine-guanine repeat expansion in the <i>ATXN2</i> gene, consistent with spinocerebellar ataxia type 2 (SCA2).</p><p><strong>Discussion: </strong>SCA2 is an autosomal dominant, degenerative disease characterized by cerebellar ataxia, including ataxic dysarthria. Our case demonstrates that SCA2 can manifest with progressive AOS. Neuroimaging supported involvement of areas classically associated with AOS.</p>","PeriodicalId":48613,"journal":{"name":"Neurology-Genetics","volume":"10 6","pages":"e200202"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606993","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":"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":"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":"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}