A doença de Alexander tipo II (AxD tipo II) é uma astrogliopatia e uma forma da doença de Alexander (AxD) caracterizada por ataxia, sintomas bulbares, paraparesia espástica, mioclonia palatal e sintomas autonômicos.
Introdução
O que você precisa saber de cara
A doença de Alexander tipo II (AxD tipo II) é uma astrogliopatia e uma forma da doença de Alexander (AxD) caracterizada por ataxia, sintomas bulbares, paraparesia espástica, mioclonia palatal e sintomas autonômicos.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
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Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 8 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 20 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição. Padrão de herança: Autosomal dominant.
GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells
Cytoplasm
Alexander disease
A rare disorder of the central nervous system. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death within the first decade. Infants with Alexander disease develop a leukodystrophy with macrocephaly, seizures, and psychomotor retardation. Patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. Histologically, Alexander disease is characterized by Rosenthal fibers, homogeneous eosinophilic inclusions in astrocytes.
Variantes genéticas (ClinVar)
264 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 176 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
2 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Doença de Alexander, tipo II
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Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
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Antibody-secreting cells (ASCs) play a central role in the pathophysiology of systemic lupus erythematosus (SLE). This single-arm, open-label, phase 2 clinical trial aims to evaluate the safety and efficacy of the ASC-depleting anti-CD38 monoclonal antibody daratumumab in patients with SLE (NCT04810754). The primary endpoint is the reduction in serum anti-double-stranded DNA (anti-dsDNA) antibody levels at week 12. Key secondary end points include safety, clinical efficacy, and immunologic changes. Ten female patients with active disease and inadequate responses to at least two immunosuppressive drugs have received eight subcutaneous injections of 1800 mg daratumumab weekly, with dexamethasone as premedication (20 mg for first two injections, then 10 mg). By week 12, anti-dsDNA antibody levels have been reduced by a median of 109.6 IU/ml (95% CI 38.1 - 274.5). The treatment resulted in rapid and sustained clinical improvements across all patients and organ domains, reflected by a 100% SRI-4 (Systemic Lupus Erythematosus Responder Index-4) response rate at week 12. Hypogammaglobulinemia occurred in 5/10 patients, requiring immunoglobulin substitution. Daratumumab treatment has depleted circulating ASCs, reduced type I interferon activity, and profoundly modulated the T-cell responses. These findings highlight the pivotal role of ASCs in SLE pathogenesis and support daratumumab as therapeutic option for SLE.
Coramitug, a Humanized Monoclonal Antibody for the Treatment of Transthyretin Amyloid Cardiomyopathy: A Phase 2, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial.
Transthyretin amyloidosis with cardiomyopathy is a progressive disease caused by the deposition of transthyretin (TTR) as amyloid in the myocardium. Current therapies may slow disease progression but do not clear existing deposits. Coramitug is a humanized monoclonal antibody that targets misfolded transthyretin, designed to promote clearance of transthyretin amyloid through antibody-mediated phagocytosis. This phase 2, double-blind, placebo-controlled trial randomized participants with transthyretin amyloidosis with cardiomyopathy to receive infusions every 4 weeks of either coramitug at 2 dosages (10 mg/kg or 60 mg/kg) or placebo in a 1:1:1 ratio for 52 weeks. The primary end points were the change from baseline to week 52 in the 6-minute walk test and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Safety was assessed for up to 64 weeks by assessing treatment-emergent adverse events, all-cause mortality, and number of cardiovascular events (comprising hospitalization caused by cardiovascular events or urgent heart failure visits). In total, 104 participants (median age, 77 years; 93% men; 84% New York Heart Association class II; 13% with variant transthyretin amyloidosis with cardiomyopathy) were randomized and dosed: 34 to 10 mg/kg of coramitug, 35 to 60 mg/kg of coramitug, and 35 to placebo. Median NT-proBNP was 1985 pg/mL (interquartile range, 1224, 3406). In total, 90% of participants were receiving disease-modifying therapy; 84% were treated with tafamidis and 7 (6.7%) with transthyretin silencers (patisiran, n=4; vutrisiran, n=3). From baseline to week 52, 60 mg/kg of coramitug significantly reduced NT-proBNP levels compared with placebo (-48% [95% CI, -65% to -22%]; P=0.0017). The change in 6-minute walk test from baseline to week 52 was not statistically different from placebo with either dose. Coramitug (60 mg/kg) was associated with improved functional echocardiographic parameters and was well tolerated. This phase 2 trial showed that coramitug, an antibody targeting misfolded transthyretin in transthyretin amyloidosis with cardiomyopathy, was well tolerated and, at a dose of 60 mg/kg, resulted in a statistically significant reduction in NT-proBNP, a validated marker of disease progression, with no statistically significant effect on 6-minute walk test within 52 weeks. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05442047.
Differences in Prevalence and Severity of Liver Disease Between Lateral Tunnel and Extracardiac Conduit Fontan.
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Variability in BIA-Derived Muscle Mass Estimates: Device Choice Impacts Diagnostic Classification.
Background/Objectives: Although discrepancies between bioelectrical impedance analysis (BIA) devices are well documented, their clinical relevance in vulnerable populations remains unclear. This study aims to assess the impact of device choice on muscle mass classification criteria in patients with cancer or obesity and to identify modifiers of device variability. Methods: BIA data from 224 adults (85 with cancer, 139 with obesity) measured with two segmental multi-frequency devices (seca mBCA 515 and InBody 970) were analyzed. Device differences were assessed using the Wilcoxon signed-rank test and agreement analyses. Differences in classification of body composition cut-offs cited in the GLIM criteria for malnutrition and the ESPEN and EASO criteria for sarcopenic obesity were evaluated using McNemar's test. The impact of disease type, sex, and age on device differences was examined through multivariable models. Results: Significant device differences were found for all parameters (all p ≤ 0.005). Discrepancies were largest for skeletal muscle mass (kg and %), with effect sizes r > 0.8 and poor agreement (Lin's CCC < 0.90). A significant impact of device choice on muscle mass classification was observed for both cancer and obesity patients (p < 0.001), with seca classifying more patients as having low fat-free mass (50% vs. 20%) and as having a body composition consistent with sarcopenic obesity (90% vs. 50%) than InBody. Discrepancies were more pronounced in cancer patients and females. Conclusions: Muscle mass assessment by BIA is highly dependent on device choice, potentially leading to clinically relevant discrepancies in classification when rigid cut-offs are applied. An individualized interpretation of BIA data and further validation of prediction equations in disease-specific subpopulations is warranted.
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CirculationComparison of matched sibling, unrelated and haploidentical donors in hematopoietic stem cell transplantation. A real-world experience from the Argentine Group for Bone Marrow Transplantation and Cell Therapy (GATMO-TC).
MedicinaThe Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer.
British journal of cancerState-of-the-art genome inference in the human MHC.
The international journal of biochemistry & cell biologyPlasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10.
PeptidesRationale and design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction.
American heart journalPrecise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial.
Clinical geneticsProtein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development.
The Journal of clinical investigationEffects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials.
The lancet. Diabetes & endocrinologyObinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis.
International journal of molecular sciencesThe EphA4 Signaling is Anti-catabolic in Synoviocytes but Pro-anabolic in Articular Chondrocytes.
Calcified tissue internationalHas the Affordable Care Act Been Associated with Increased Insurance Coverage and Early-stage Diagnoses of Bone and Soft-tissue Sarcomas in Adults?
Clinical orthopaedics and related researchCrescentic glomerulonephritis: what's different in South Asia? A single center observational cohort study.
Wellcome open researchThe impact of donor type on the outcome of pediatric patients with very high risk acute lymphoblastic leukemia. A study of the ALL SCT 2003 BFM-SG and 2007-BFM-International SG.
Bone marrow transplantationNatural Products as Modulators of Sirtuins.
Molecules (Basel, Switzerland)Class switching and high-affinity immunoglobulin G production by B cells is dispensable for the development of hypertension in mice.
Cardiovascular researchRelevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice.
VirulenceAtezolizumab plus modified docetaxel-cisplatin-5-fluorouracil (mDCF) regimen versus mDCF in patients with metastatic or unresectable locally advanced recurrent anal squamous cell carcinoma: a randomized, non-comparative phase II SCARCE GERCOR trial.
BMC cancerThe Effect of Biochars and Endophytic Bacteria on Growth and Root Rot Disease Incidence of Fusarium Infested Narrow-Leafed Lupin (Lupinus angustifolius L.).
MicroorganismsDiscovery and Differential Processing of HLA Class II-Restricted Minor Histocompatibility Antigen LB-PIP4K2A-1S and Its Allelic Variant by Asparagine Endopeptidase.
Frontiers in immunologyNovel Biomarkers in Patients with Chronic Kidney Disease: An Analysis of Patients Enrolled in the GCKD-Study.
Journal of clinical medicineDevelopment of 18F-Fluoroglycosylated PSMA-Ligands with Improved Renal Clearance Behavior.
Molecular pharmaceuticsGlycochenodeoxycholate Promotes Liver Fibrosis in Mice with Hepatocellular Cholestasis.
CellsInfantile Alexander Disease with Late Onset Infantile Spasms and Hypsarrhythmia.
Balkan journal of medical genetics : BJMGEffects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological AssociationNO• /RUNX3/kynurenine metabolic signaling enhances disease aggressiveness in pancreatic cancer.
International journal of cancerSystemic AAV8-mediated delivery of a functional copy of muscle glycogen phosphorylase (Pygm) ameliorates disease in a murine model of McArdle disease.
Human molecular geneticsQuorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant Staphylococcus aureus Isolates.
mSphereNOX2 mediates quiescent handling of dead cell remnants in phagocytes.
Redox biologyTransplantation in Children and Adolescents with Acute Lymphoblastic Leukemia from a Matched Donor versus an HLA-Identical Sibling: Is the Outcome Comparable? Results from the International BFM ALL SCT 2007 Study.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow TransplantationElevated Insulin and Insulin Resistance are Associated with Altered Myelin in Cognitively Unimpaired Middle-Aged Adults.
Obesity (Silver Spring, Md.)A Phase 2 Study of Galunisertib (TGF-β1 Receptor Type I Inhibitor) and Sorafenib in Patients With Advanced Hepatocellular Carcinoma.
Clinical and translational gastroenterologyDo Nonsuicidal Severely Depressed Individuals with Diabetes Profit from Internet-Based Guided Self-Help? Secondary Analyses of a Pragmatic Randomized Trial.
Journal of diabetes researchHeat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell-killing capability.
JCI insightHybrid Coronary Percutaneous Treatment with Metallic Stents and Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-years Results from the GABI-R Registry.
Journal of clinical medicineRANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass.
The Journal of clinical investigationPrognostic relevance of topoisomerase II α and minichromosome maintenance protein 6 expression in colorectal cancer.
BMC cancerA novel mutation in the GFAP gene expands the phenotype of Alexander disease.
Journal of medical geneticsCardiovascular outcomes and achieved blood pressure in patients with and without diabetes at high cardiovascular risk.
European heart journalMyD88 Is Required for Efficient Control of Coxiella burnetii Infection and Dissemination.
Frontiers in immunologyA Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB).
Clinical cancer research : an official journal of the American Association for Cancer ResearchContribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases.
Biological psychiatryMesenchymal stem cell dysfunction in diabetes.
Molecular biology reportsInfluence of the surgical technique on survival in the treatment of carcinomas of the true cardia (Siewert Type II) - Right thoracoabdominal vs. transhiatal-abdominal approach.
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical OncologySize-dependent functional response of Xenopus laevis feeding on mosquito larvae.
PeerJGFAP canonical transcript may not be suitable for the diagnosis of adult-onset Alexander disease.
Acta neuropathologica communicationsImmunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer.
Clinical cancer research : an official journal of the American Association for Cancer ResearchIs exon 8 the most critical or the only dispensable exon of the VCAN gene? Insights into VCAN variants and clinical spectrum of Wagner syndrome.
American journal of medical genetics. Part APrognostic significance of atrial fibrillation in acute decompensated heart failure with reduced versus preserved ejection fraction.
Clinical research in cardiology : official journal of the German Cardiac SocietyConfounding influence of tamoxifen in mouse models of Cre recombinase-induced gene activity or modulation.
Archives of toxicologyExpansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease.
GutMannan-induced Nos2 in macrophages enhances IL-17-driven psoriatic arthritis by innate lymphocytes.
Science advancesAllogeneic Stem Cell Transplantation from HLA-Mismatched Donors for Pediatric Patients with Acute Lymphoblastic Leukemia Treated According to the 2003 BFM and 2007 International BFM Studies: Impact of Disease Risk on Outcomes.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow TransplantationTRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.
Pflugers Archiv : European journal of physiologyMesenchymal TNFR2 promotes the development of polyarthritis and comorbid heart valve stenosis.
JCI insightLong-term follow-up of HIV-1-infected adults who received the F4/AS01B HIV-1 vaccine candidate in two randomised controlled trials.
VaccineCan genetic testing guide the therapy of cholestatic pruritus? A case of benign recurrent intrahepatic cholestasis type 2 with severe nasobiliary drainage-refractory itch.
Hepatology communications[Chronic heart failure in older patients : Updated national healthcare guidelines on chronic heart failure from a geriatric perspective].
Zeitschrift fur Gerontologie und GeriatrieThyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function.
Nature medicineThe Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update.
NutrientsMoonlighting newborn screening markers: the incidental discovery of a second-tier test for Pompe disease.
Genetics in medicine : official journal of the American College of Medical GeneticsRandomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial-rationale and study protocol.
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic SurgeryTHP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila - a systems biology study.
Scientific reportsDiabetic retinopathy: Breaking the barrier.
Pathophysiology : the official journal of the International Society for PathophysiologyPost-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats.
PloS oneIncreased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia.
Hypertension (Dallas, Tex. : 1979)Hyperglycemia and dyslipidemia of Isabela, Galápagos, Ecuador: A pilot study of cardiovascular risk factors in an Isolated Island community.
Diabetes research and clinical practiceA Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells.
Cell reportsEarly energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.
Chemico-biological interactionsProspective Study of Cetuximab, Carboplatin, and Radiation Therapy for Patients With Locally Advanced Head and Neck Squamous Cell Cancer Unfit for Cisplatin.
International journal of radiation oncology, biology, physicsConcomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen.
Journal of immunology (Baltimore, Md. : 1950)Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis.
Proceedings of the National Academy of Sciences of the United States of AmericaSoluble Urokinase-Type Plasminogen Activator Receptor Improves Risk Prediction in Patients With Chronic Heart Failure.
JACC. Heart failureAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Daratumumab in systemic lupus erythematosus: a single-arm phase 2 trial.
- Coramitug, a Humanized Monoclonal Antibody for the Treatment of Transthyretin Amyloid Cardiomyopathy: A Phase 2, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial.
- Differences in Prevalence and Severity of Liver Disease Between Lateral Tunnel and Extracardiac Conduit Fontan.
- Variability in BIA-Derived Muscle Mass Estimates: Device Choice Impacts Diagnostic Classification.
- Development of Radiomics Models to Predict Progression-Free Survival and Early Polymetastatic Progression in Patients With Lung Oligometastases Treated on the Single-Arm Phase II Stereotactic Ablative Radiotherapy-5 Trial.
- Re: Chase Peng Yun Ng, Alexander Light, Sai Kalpitha Eragamreddy, et al. Five-year Outcomes for Men after Negative Magnetic Resonance Imaging (MRI) or Negative Biopsy in the RAPID MRI-directed Prostate Cancer Diagnostic Pathway. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2025.10.015.
- The dominance of large-scale phase dynamics in human cortex, from delta to gamma.
- Four new species of Dasymallomyia Brunetti (Diptera, Limoniidae, Chioneinae) from China.
- Gross anatomy of the skeleton of neonates of the Orinoco Matamata turtle (Chelus orinocensis).
- Defining the Prominent Ear: Anthropometric Profile of Prominent and Normal Ears in the Arabian Peninsula.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:363722(Orphanet)
- MONDO:0018210(MONDO)
- GARD:17573(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q55346030(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
