A Esclerose Lateral Amiotrófica Juvenil (JALS) é uma doença muito rara e grave que afeta os nervos que controlam os movimentos. Ela é caracterizada pela perda progressiva desses nervos, tanto os que vêm do cérebro quanto os da medula espinhal, o que causa rigidez muscular no rosto, dificuldade para falar (disartria) e problemas para andar. Os primeiros sintomas surgem antes dos 25 anos de idade.
Introdução
O que você precisa saber de cara
A Esclerose lateral amiotrófica juvenil é uma doença rara que enfraquece progressivamente os músculos responsáveis pelos movimentos e pela fala antes dos 25 anos de idade. Com o passar do tempo, ela costuma causar rigidez muscular, dificuldades para engolir e limitações importantes para caminhar. Para o tratamento no Brasil, o Sistema Único de Saúde (SUS) dispensa o medicamento Riluzol de 50 mg por meio da farmácia de alto custo. Além disso, a rede pública oferece procedimentos de reabilitação motora e exames genéticos como o exoma para investigar e acompanhar o quadro.
A Esclerose Lateral Amiotrófica Juvenil (JALS) é uma doença muito rara e grave que afeta os nervos que controlam os movimentos. Ela é caracterizada pela perda progressiva desses nervos, tanto os que vêm do cérebro quanto os da medula espinhal, o que causa rigidez muscular no rosto, dificuldade para falar (disartria) e problemas para andar. Os primeiros sintomas surgem antes dos 25 anos de idade.
Tem tratamento?
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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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 25 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 77 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
5 genes identificados com associação a esta condição. Padrão de herança: Autosomal recessive.
Amyotrophic lateral sclerosis 2
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
Amyotrophic lateral sclerosis 27, juvenile
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS27 is an autosomal dominant form manifesting as toe walking and gait abnormalities in early childhood.
Spastic paraplegia 11, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Amyotrophic lateral sclerosis 16, juvenile
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
Variantes genéticas (ClinVar)
390 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 15 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
8 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 — Esclerose lateral amiotrófica juvenil
Selecione um estado ou use sua localização para ver resultados.
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
An Unusual Presentation of Juvenile Amyotrophic Lateral Sclerosis with Superoxide Dismutase 1 Mutation: Subacute Bulbar Palsy With Asymmetric Limb Weakness.
SIGMAR1 gene-related neuromuscular disorders - what do we know?
Distal hereditary motor neuropathies (dHMNs) are a clinically and genetically diverse group of rare neuromuscular disorders characterized by progressive distal muscle weakness and atrophy, often with early onset and sparing of sensory function. One subtype, Jerash-type dHMN (dHMNJ), is caused by biallelic mutations in the SIGMAR1 gene and presents with pyramidal signs in addition to distal weakness. A literature review was conducted by searches of the MEDLINE and PubMed databases using selected terms. Relevant original articles, case reports, case series, and reviews were selected as data sources. SIGMAR1-related disorders (SIGMAR1-RD) encompass a broad clinical spectrum including dHMN and juvenile amyotrophic lateral sclerosis (ALS) phenotypes. The Sigma-1 receptor plays a key role in cellular stress responses, ER-mitochondria interaction, and neuronal survival. Clinical presentation often includes distal muscle weakness and atrophy with pyramidal signs. We present a 12-year-old boy with distal muscle weakness, foot drop, and pyramidal signs. Genetic testing identified a homozygous c.247T > C (p.Phe83Leu) SIGMAR1 variant, previously classified as a variant of uncertain significance (VUS). This article supports the pathogenicity of the c.247T > C (p.Phe83Leu) SIGMAR1 variant and underlines the need for broader genetic testing in hereditary motor neuropathies.
A novel heterozygous variant of FUS gene associated with juvenile ALS and premature tremor onset: a case report.
Juvenile amyotrophic lateral sclerosis (JALS) is neurodegenerative disease of the upper and lower motor neurons of rare incidence. Although fused in sarcoma (FUS) mutations in JALS patients have been associated with movement disorders, here we described the case of a young girl with very early onset of tremor, years before commencement of weakness; once symptoms of JALS were stablished, a typical rapid disease progression from spinal to bulbar symptoms were noticed. Genetic testing revealed a novel mutation in FUS gene causative of a protein dysfunction. This case emphasizes the fact that some mutations within the FUS in JALS patients may produce a symptom onset with tremor.
SYNE1 Deficiency Manifesting Primarily With Motor Neuron Disease.
SYNE1 deficiency is an autosomal recessive disorder with a broad phenotypic spectrum, most commonly presenting as adult-onset cerebellar ataxia with or without motor neuron dysfunction. We aimed to expand this spectrum by describing the clinical and genetic findings in 2 unrelated families with early-onset motor neuron disease and virtually no cerebellar signs over time. We performed detailed clinical, neurophysiologic, and genetic studies of 2 unrelated families with juvenile amyotrophic lateral sclerosis (ALS) and biallelic variants in SYNE1. The phenotypes of both families showed onset of symptoms in childhood or adolescence, with signs of upper and lower motor neuron dysfunction in multiple territories suggestive of juvenile ALS. Patients developed progressive muscle weakness, eventually leading to respiratory distress and bulbar signs. Whole-exome sequencing identified SYNE1 biallelic truncating variants in both families: a homozygous nonsense variant, c.23131C>T (p.Gln7711*), in Family 1, and a novel homozygous splice-site variant, c.17851-1G>A, in Family 2. Notably, mild or no cerebellar manifestations were observed during the follow-up. This report highlights a novel phenotype of SYNE1 deficiency characterized by early-onset motor neuron disease and virtually no cerebellar manifestations, broadening the phenotypic spectrum of this complex neurodegenerative disease. These findings support investigating SYNE1 variants in juvenile ALS and including SYNE1 in motor neuron disease gene panels.
Pathology of three ALS patients with FUS variants, including one likely benign Q23L variant lacking FUS inclusions.
Fused in sarcoma (FUS) is an RNA-binding protein implicated in juvenile amyotrophic lateral sclerosis (ALS). Mutations in the FUS gene, particularly those affecting the nuclear localization signal (NLS), impair nuclear import and lead to cytoplasmic accumulation of FUS inclusions in motor neurons. However, the pathological and clinical significance of FUS variants outside the NLS remains less understood. Here, we describe clinical and histopathological findings from three ALS patients carrying FUS variants: two with NLS-region variants (R495X and P525L), and one with a variant in the N-terminal region outside the NLS (Q23L). The patients carrying NLS variants presented with aggressive, juvenile-onset spinal and bulbar ALS, characterized primarily by lower motor neuron involvement and rapid disease progression. In contrast, the Q23L patient exhibited a slowly progressive disease course, with predominantly upper motor neuron signs. Neuropathological analysis revealed cytoplasmic FUS inclusions in motor neurons of patients with NLS variants, consistent with typical FUS pathology. In contrast, the Q23L patient lacked FUS inclusions and instead displayed pTDP-43 pathology in the hippocampus, neocortex (including the motor cortex), nucleus olivaris, lentiform nucleus, striatum, and some lower motor neurons. Taken together, these results suggest that Q23L is most likely a benign variant. As antisense oligonucleotides (ASOs) targeting FUS are currently being explored in clinical trials, further neuropathological investigations are needed to determine whether ASO-mediated FUS silencing would be effective for patients carrying FUS variants outside the NLS region.
Publicações recentes
An Unusual Presentation of Juvenile Amyotrophic Lateral Sclerosis with Superoxide Dismutase 1 Mutation: Subacute Bulbar Palsy With Asymmetric Limb Weakness.
Gne deletion in adult mice can cause thrombocytopenia, anemia, myopathy, bleeding, and death.
SIGMAR1 gene-related neuromuscular disorders - what do we know?
SYNE1 Deficiency Manifesting Primarily With Motor Neuron Disease.
Acquired hemophilia a in a female with minimal change disease and hypothyroidism: a rare case report.
📚 EuropePMC72 artigos no totalmostrando 69
An Unusual Presentation of Juvenile Amyotrophic Lateral Sclerosis with Superoxide Dismutase 1 Mutation: Subacute Bulbar Palsy With Asymmetric Limb Weakness.
Annals of Indian Academy of NeurologyGne deletion in adult mice can cause thrombocytopenia, anemia, myopathy, bleeding, and death.
Journal of neuromuscular diseasesSIGMAR1 gene-related neuromuscular disorders - what do we know?
Neurologia i neurochirurgia polskaSYNE1 Deficiency Manifesting Primarily With Motor Neuron Disease.
Neurology. GeneticsAcquired hemophilia a in a female with minimal change disease and hypothyroidism: a rare case report.
Annals of medicine and surgery (2012)Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin gene.
Journal of applied geneticsPathology of three ALS patients with FUS variants, including one likely benign Q23L variant lacking FUS inclusions.
Human molecular geneticsA novel heterozygous variant of FUS gene associated with juvenile ALS and premature tremor onset: a case report.
Amyotrophic lateral sclerosis & frontotemporal degenerationA case of rapidly progressive juvenile amyotrophic lateral sclerosis associated with a pathogenetic heterozygous de novo variant in the FUS gene.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyA novel SIGMAR1 missense mutation leads to distal hereditary motor neuropathy phenotype mimicking juvenile ALS: a case report of China.
Frontiers in geneticsMultiomics Approach Reveal Novel Insights in FUS Driven Juvenile Amyotrophic Lateral Sclerosis: A Family Quartet Analysis.
Annals of neurosciencesGenetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral sclerosis.
Journal of neurologyPhenotype and Genotype of Children with ALS2 gene-Related Disorder.
NeuropediatricsJuvenile Amyotrophic Lateral Sclerosis: A Case Report of a Rare and Aggressive Presentation in a 22-Year-Old Filipino Male.
CureusSerine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.
Journal of neuromuscular diseasesModeling sporadic juvenile ALS in iPSC-derived motor neurons explores the pathogenesis of FUSR503fs mutation.
Frontiers in cellular neuroscienceDistal hereditary motor neuropathies.
Revue neurologiqueClinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges.
GenesRecurrent de-novo gain-of-function mutation in SPTLC2 confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis.
Journal of neurology, neurosurgery, and psychiatryAssociation of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis.
Frontiers of medicineA brief report on juvenile amyotrophic lateral sclerosis cases in the United States National ALS Registry: 2010-2018.
Amyotrophic lateral sclerosis & frontotemporal degenerationThirty-Year Follow-Up of Early Onset Amyotrophic Lateral Sclerosis with a Pathogenic Variant in SPTLC1.
Case reports in neurologySPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS.
Biochimica et biophysica acta. Molecular and cell biology of lipidsMutation screening of SPTLC1 and SPTLC2 in amyotrophic lateral sclerosis.
Human genomicsClinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations.
Chinese medical journalEarly onset hereditary neuronopathies: an update on non-5q motor neuron diseases.
Brain : a journal of neurologyA de novo c.113 T > C: p.L38R mutation of SPTLC1: case report of a girl with sporadic juvenile amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis & frontotemporal degenerationAn Atypical Presentation of Upper Motor Neuron Predominant Juvenile Amyotrophic Lateral Sclerosis Associated with TARDBP Gene: A Case Report and Review of the Literature.
GenesThe VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat.
eLifeA novel mutation in the ALS2 gene in an iranian kurdish family with juvenile amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis & frontotemporal degenerationFUS-P525L Juvenile Amyotrophic Lateral Sclerosis and Intellectual Disability: Evidence for Association and Oligogenic Inheritance.
Neurology. GeneticsProximity-based labeling reveals DNA damage-induced phosphorylation of fused in sarcoma (FUS) causes distinct changes in the FUS protein interactome.
The Journal of biological chemistryALS2-Related Motor Neuron Diseases: From Symptoms to Molecules.
BiologyJuvenile Amyotrophic Lateral Sclerosis: A Review.
GenesJuvenile amyotrophic lateral sclerosis associated with biallelic c.757delG mutation of sorbitol dehydrogenase gene.
Amyotrophic lateral sclerosis & frontotemporal degenerationThe expanding clinical and genetic spectrum of alsin-related disorders: the first cohort of Brazilian patients.
Amyotrophic lateral sclerosis & frontotemporal degenerationGeneration and characterization of an endogenously tagged SPG11-human iPSC line by CRISPR/Cas9 mediated knock-in.
Stem cell researchAssociation of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.
JAMA neurologyA rare case of juvenile amyotrophic lateral sclerosis.
The Turkish journal of pediatricsA case of juvenile-onset amyotrophic lateral sclerosis with a de novo frameshift FUS gene mutation presenting with bilateral abducens palsy.
Amyotrophic lateral sclerosis & frontotemporal degenerationThe heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment.
Neurobiology of agingGenotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations.
American journal of medical genetics. Part AUniparental Disomy Leading to a Rare Juvenile Form of ALS.
Journal of pediatrics, perinatology and child healthA Human iPSC Line Carrying a de novo Pathogenic FUS Mutation Identified in a Patient With Juvenile ALS Differentiated Into Motor Neurons With Pathological Characteristics.
Frontiers in cellular neuroscienceFUS mutation is probably the most common pathogenic gene for JALS, especially sporadic JALS.
Revue neurologiqueThe ALS-related σ1R E102Q Mutant Eludes Ligand Control and Exhibits Anomalous Response to Calcium.
International journal of molecular sciencesJuvenile amyotrophic lateral sclerosis with complex phenotypes associated with novel SYNE1 mutations.
Amyotrophic lateral sclerosis & frontotemporal degenerationA de novo c.1509dupA:p.R503fs mutation of FUS: report of a girl with sporadic juvenile amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis & frontotemporal degenerationDescription of combined ARHSP/JALS phenotype in some patients with SPG11 mutations.
Molecular genetics & genomic medicineDistinct Regulation of σ 1 Receptor Multimerization by Its Agonists and Antagonists in Transfected Cells and Rat Liver Membranes.
The Journal of pharmacology and experimental therapeuticsA juvenile ALS-like phenotype dramatically improved after high-dose riboflavin treatment.
Annals of clinical and translational neurologyChinese families with autosomal recessive hereditary spastic paraplegia caused by mutations in SPG11.
BMC neurologyA juvenile sporadic amyotrophic lateral sclerosis case with P525L mutation in the FUS gene: A rare co-occurrence of autism spectrum disorder and tremor.
Journal of the neurological sciencesClinical and Genetic Features of Patients with Juvenile Amyotrophic Lateral Sclerosis with Fused in Sarcoma (FUS) Mutation.
Medical science monitor : international medical journal of experimental and clinical researchClinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologySIGMAR1 gene mutation causing Distal Hereditary Motor Neuropathy in a Portuguese family.
Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of MyologyA novel SETX gene mutation associated with Juvenile amyotrophic lateral sclerosis.
Brain and behaviorThe investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis.
Clinical geneticsA novel mutation of BICD2 gene associated with juvenile amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis & frontotemporal degenerationA Novel Missense Mutation of the DDHD1 Gene Associated with Juvenile Amyotrophic Lateral Sclerosis.
Frontiers in aging neuroscienceMitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS.
EMBO molecular medicineMitochondrial Membrane Protein-Associated Neurodegeneration Mimicking Juvenile Amyotrophic Lateral Sclerosis.
Pediatric neurologyJuvenile amyotrophic lateral sclerosis: Classical wine glass sign on magnetic resonance imaging.
Journal of pediatric neurosciencesDe novo FUS P525L mutation in Juvenile amyotrophic lateral sclerosis with dysphonia and diplopia.
Neurology. GeneticsTurkish families with juvenile motor neuron disease broaden the phenotypic spectrum of SPG11.
Neurology. GeneticsCLEC4C p.K210del variant causes impaired cell surface transport in plasmacytoid dendritic cells of amyotrophic lateral sclerosis.
OncotargetUtility of whole exome sequencing in evaluation of juvenile motor neuron disease.
Muscle & nerveIdentification of two novel ALS2 mutations in infantile-onset ascending hereditary spastic paraplegia.
Amyotrophic lateral sclerosis & frontotemporal degenerationALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.
Brain : a journal of neurologyAssociações
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Doença com base genética
Um médico geneticista pode ajudar no diagnóstico de Esclerose lateral amiotrófica juvenil e no aconselhamento genético da família.
Doenças relacionadas
Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico
Perguntas frequentes
O que as famílias mais perguntam sobre esta doença — cada resposta com a fonte de onde saiu
Existe um documento oficial para "Esclerose Lateral Amiotrófica". Ele pode não cobrir esta forma específica da doença — confira no texto do protocolo antes de contar com ele.
A Esclerose lateral amiotrófica juvenil é uma doença rara que compromete os neurônios motores responsáveis pelos movimentos corporais. Diferente de outras apresentações, o início de suas manifestações ocorre antes dos 25 anos de vida, frequentemente durante a infância.
Referências
Fontes citadas no texto, publicações do grafo e bases de dados usadas neste verbete
7 publicações do grafo RarasNet (PubMed) · 6 bases de dados. Títulos, periódicos e PMIDs vêm direto da fonte, sem intermediação de IA.
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.
Citar este verbete
Raras. (s.d.). Esclerose lateral amiotrófica juvenil. Em Raras — Enciclopédia de Doenças Raras do Brasil. https://raras.org/doenca/esclerose-lateral-amiotrofica-juvenil
Formato APA. Conteúdo sob CC BY 4.0 — reuso livre com atribuição.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
Esclerose lateral amiotrófica juvenil
📋 Origem dos dados
Esta página agrega dados de fontes públicas e oficiais. Dados sobre cobertura no SUS (PCDT, CEAF) são verificados ativamente por agente proativo (ver badge no infobox). Demais dados têm atribuição de fonte + data da última sincronização — clique para abrir o original.
- Doença rara (ontologia)
- fonte: Orphanet
- Identificador unificado
- fonte: MONDO
- Codificação WHO/SUS
- fonte: WHO ICD-10 / DATASUS
- NIH/GARD
- fonte: GARD (NIH)
- Dado público estruturado
- fonte: Wikidata
