Raras
Buscar doenças, sintomas, genes...
Ataxia espástica
ORPHA:316226CID-10 · G11.4DOENÇA RARA

A síndrome Strumpell-Lorrain, ou Paraparesia espástica familiar, é um grupo de doenças hereditárias, cuja principal característica é a rigidez progressiva e contração (espasticidade) nos membros inferiores, como resultado de uma lesão ou disfunção dos nervos.

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Introdução

O que você precisa saber de cara

📋

Ataxia espástica é uma doença neurológica rara caracterizada por marcha espástica, amiotrofia e atraso global grave do desenvolvimento. Pode apresentar morfologia anormal da pálpebra, propriocepção prejudicada e fasciculações. Associada a alterações genéticas como GLRX5 e AFG3L2.

Pesquisas ativas
2 ensaios
6 total registrados no ClinicalTrials.gov
Publicações científicas
551 artigos
Último publicado: 2026 Apr 9
🏥
SUS: Sem cobertura SUSScore: 0%
CID-10: G11.4
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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🧠
Neurológico
62 sintomas
👁️
Olhos
16 sintomas
💪
Músculos
13 sintomas
🦴
Ossos e articulações
12 sintomas
😀
Face
4 sintomas
👂
Ouvidos
4 sintomas

+ 78 sintomas em outras categorias

Características mais comuns

Morfologia anormal da pálpebra
Propriocepção prejudicada
Hiperglicinemia não cetótica
Aumento da concentração de glicina no LCR
Cisto aracnoide
Amiotrofia generalizada
200sintomas
Sem dados (200)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 200 características clínicas mais associadas, ordenadas por frequência.

Morfologia anormal da pálpebraAbnormal eyelid morphology
Propriocepção prejudicadaImpaired proprioception
Hiperglicinemia não cetóticaNonketotic hyperglycinemia
Aumento da concentração de glicina no LCRIncreased CSF glycine concentration
Cisto aracnoideArachnoid cyst

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2026
Total histórico551PubMed
Últimos 10 anos200publicações
Pico202444 papers
Linha do tempo
2026Hoje · 2026🧪 2004Primeiro ensaio clínico📈 2024Ano de pico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

11 genes identificados com associação a esta condição.

GLRX5Glutaredoxin-related protein 5, mitochondrialDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer (PubMed:20364084, PubMed:23615440). Receives 2Fe/2S clusters from scaffold protein ISCU and mediates their transfer to apoproteins, to the 4Fe/FS cluster biosynthesis machinery, or export from mitochondrion (PubMed:20364084, PubMed:23615440, PubMed:24334290). Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1 (PubMed:20364084)

LOCALIZAÇÃO

Mitochondrion matrix

VIAS BIOLÓGICAS (1)
Mitochondrial iron-sulfur cluster biogenesis
MECANISMO DE DOENÇA

Anemia, sideroblastic, 3, pyridoxine-refractory

A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA3 is refractory to treatment with vitamin B6, while iron chelation therapy may result in clinical improvement. SIDBA3 inheritance is autosomal recessive.

EXPRESSÃO TECIDUAL(Ubíquo)
Testículo
65.0 TPM
Glândula adrenal
55.8 TPM
Músculo esquelético
48.2 TPM
Ovário
43.3 TPM
Rim - Medula
42.5 TPM
OUTRAS DOENÇAS (2)
spasticity-ataxia-gait anomalies syndromesideroblastic anemia 3
HGNC:20134UniProt:Q86SX6
COQ4Ubiquinone biosynthesis protein COQ4 homolog, mitochondrialDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Lyase that catalyzes the C1-decarboxylation of 4-hydroxy-3-methoxy-5-(all-trans-decaprenyl)benzoic acid into 2-methoxy-6-(all-trans-decaprenyl)phenol during ubiquinone biosynthesis

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (1)
Ubiquinol biosynthesis
MECANISMO DE DOENÇA

Coenzyme Q10 deficiency, primary, 7

An autosomal recessive disorder resulting from mitochondrial dysfunction and characterized by decreased levels of coenzyme Q10, and severe cardiac or neurologic symptoms soon after birth, usually resulting in death. Rarely, symptoms may have later onset.

VIAS REACTOME (1)
OUTRAS DOENÇAS (2)
spastic ataxia 10, autosomal recessiveneonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome
HGNC:19693UniProt:Q9Y3A0
VAMP1Vesicle-associated membrane protein 1Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Involved in the targeting and/or fusion of transport vesicles to their target membrane

LOCALIZAÇÃO

Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membraneSynapse, synaptosomeCytoplasmic vesicle membraneMitochondrion outer membrane

VIAS BIOLÓGICAS (3)
Toxicity of botulinum toxin type F (botF)Toxicity of botulinum toxin type D (botD)Toxicity of botulinum toxin type G (botG)
MECANISMO DE DOENÇA

Spastic ataxia 1, autosomal dominant

An autosomal dominant form of spastic ataxia, a progressive neurodegenerative disorder characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance.

EXPRESSÃO TECIDUAL(Ubíquo)
Brain Frontal Cortex BA9
106.3 TPM
Brain Spinal cord cervical c-1
80.7 TPM
Córtex cerebral
61.8 TPM
Baço
56.5 TPM
Tireoide
56.0 TPM
OUTRAS DOENÇAS (2)
myasthenic syndrome, congenital, 25, presynapticspastic ataxia 1
HGNC:12642UniProt:P23763
AFG3L2Mitochondrial inner membrane m-AAA protease component AFG3L2Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development (PubMed:19748354, PubMed:28396416, PubMed:29932645, PubMed:30683687, PubMed:31327635, PubMed:37917749, PubMed:38157846). AFG3L2 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small pe

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (2)
Processing of SMDT1Mitochondrial protein degradation
MECANISMO DE DOENÇA

Spinocerebellar ataxia 28

Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment.

OUTRAS DOENÇAS (3)
optic atrophy 12spinocerebellar ataxia type 28spastic ataxia 5
HGNC:315UniProt:Q9Y4W6
GLSGlutaminase kidney isoform, mitochondrialCandidate gene tested inRestrito
FUNÇÃO

Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate, the main excitatory neurotransmitter in the brain (PubMed:30239721, PubMed:30575854, PubMed:30970188) Lacks catalytic activity

LOCALIZAÇÃO

MitochondrionCytoplasm, cytosolMitochondrion matrix

VIAS BIOLÓGICAS (3)
Glutamate and glutamine metabolismGlutamate Neurotransmitter Release CycleTP53 Regulates Metabolic Genes
MECANISMO DE DOENÇA

Developmental and epileptic encephalopathy 71

A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE71 is an autosomal recessive form with onset at birth. Death occurs in first weeks of life.

EXPRESSÃO TECIDUAL(Ubíquo)
Aorta
108.5 TPM
Cérebro - Hemisfério cerebelar
92.8 TPM
Linfócitos
90.6 TPM
Artéria tibial
88.3 TPM
Brain Frontal Cortex BA9
76.9 TPM
OUTRAS DOENÇAS (4)
global developmental delay, progressive ataxia, and elevated glutaminedevelopmental and epileptic encephalopathy, 71infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual developmentspastic ataxia-dysarthria due to glutaminase deficiency
HGNC:4331UniProt:O94925
MTPAPPoly(A) RNA polymerase, mitochondrialDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Polymerase that creates the 3' poly(A) tail of mitochondrial transcripts. Can use all four nucleotides, but has higher activity with ATP and UTP (in vitro). Plays a role in replication-dependent histone mRNA degradation. May be involved in the terminal uridylation of mature histone mRNAs before their degradation is initiated. Might be responsible for the creation of some UAA stop codons which are not encoded in mtDNA

LOCALIZAÇÃO

CytoplasmMitochondrion

VIAS BIOLÓGICAS (1)
Mitochondrial mRNA modification
MECANISMO DE DOENÇA

Spastic ataxia 4, autosomal recessive

A slowly progressive neurodegenerative disease characterized by cerebellar ataxia, spastic paraparesis, dysarthria, and optic atrophy.

EXPRESSÃO TECIDUAL(Ubíquo)
Testículo
25.1 TPM
Linfócitos
11.8 TPM
Nervo tibial
10.6 TPM
Cervix Endocervix
10.3 TPM
Útero
10.0 TPM
OUTRAS DOENÇAS (1)
spastic ataxia 4
HGNC:25532UniProt:Q9NVV4
KIF1CKinesin-like protein KIF1CDisease-causing germline mutation(s) inRestrito
FUNÇÃO

Motor required for the retrograde transport of Golgi vesicles to the endoplasmic reticulum. Has a microtubule plus end-directed motility

LOCALIZAÇÃO

Cytoplasm, cytoskeleton

VIAS BIOLÓGICAS (2)
KinesinsCOPI-dependent Golgi-to-ER retrograde traffic
MECANISMO DE DOENÇA

Spastic ataxia 2, autosomal recessive

A neurologic disorder characterized by cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. Cognition is not affected.

EXPRESSÃO TECIDUAL(Ubíquo)
Músculo esquelético
308.2 TPM
Brain Spinal cord cervical c-1
252.4 TPM
Substância negra
164.6 TPM
Artéria tibial
160.2 TPM
Aorta
151.4 TPM
OUTRAS DOENÇAS (1)
spastic ataxia 2
HGNC:6317UniProt:O43896
SACSSacsinDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins

LOCALIZAÇÃO

Cytoplasm

MECANISMO DE DOENÇA

Spastic ataxia Charlevoix-Saguenay type

A neurodegenerative disease characterized by early-onset cerebellar ataxia, spasticity, retinal hypermyelination, pyramidal signs, and both axonal and demyelinating neuropathy with loss of sensory nerve conduction and reduced motor conduction velocities. Other features include dysarthria, distal muscle wasting, nystagmus, defect in conjugate pursuit ocular movements, retinal striation (from prominent retinal nerves) obscuring the retinal blood vessels in places, and the frequent presence of mitral valve prolapse.

EXPRESSÃO TECIDUAL(Ubíquo)
Fibroblastos
22.6 TPM
Linfócitos
15.5 TPM
Artéria tibial
13.4 TPM
Aorta
13.3 TPM
Artéria coronária
13.1 TPM
INTERAÇÕES PROTEICAS (1)
OUTRAS DOENÇAS (1)
Charlevoix-Saguenay spastic ataxia
HGNC:10519UniProt:Q9NZJ4
CHP1Calcineurin B homologous protein 1Disease-causing germline mutation(s) inModerado
FUNÇÃO

Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regul

LOCALIZAÇÃO

NucleusCytoplasmCytoplasm, cytoskeletonEndomembrane systemEndoplasmic reticulum-Golgi intermediate compartmentEndoplasmic reticulumCell membraneMembrane

VIAS BIOLÓGICAS (1)
Hyaluronan degradation
MECANISMO DE DOENÇA

Spastic ataxia 9, autosomal recessive

An autosomal recessive disorder characterized by onset of spastic ataxia in the first years of life. Clinical features include motor neuropathy, cerebellar atrophy, spastic paraparesis, intellectual disability, slow ocular saccades, axial hypotonia, distal muscle weakness and atrophy, and pyramidal symptoms, including hyperreflexia and extensor plantar responses.

VIAS REACTOME (1)
OUTRAS DOENÇAS (1)
spastic ataxia 9, autosomal recessive
HGNC:HGNC:17433UniProt:Q99653
MARS2Methionine--tRNA ligase, mitochondrialDisease-causing germline mutation(s) inTolerante
LOCALIZAÇÃO

Mitochondrion matrix

VIAS BIOLÓGICAS (1)
Mitochondrial tRNA aminoacylation
MECANISMO DE DOENÇA

Spastic ataxia 3, autosomal recessive

A neurologic disorder characterized by cerebellar ataxia, ataxic gait, spasticity, and hyperreflexia. Other variable features include dysarthria, dysmetria, mild cognitive impairment, urinary urgency and dystonic positioning.

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
25.8 TPM
Esôfago - Mucosa
7.7 TPM
Baço
7.5 TPM
Fibroblastos
7.2 TPM
Glândula adrenal
7.2 TPM
OUTRAS DOENÇAS (2)
spastic ataxia 3combined oxidative phosphorylation defect type 25
HGNC:25133UniProt:Q96GW9
NKX6-2Homeobox protein Nkx-6.2Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Transcription factor with repressor activity involved in the regulation of axon-glial interactions at myelin paranodes in oligodendrocytes. Binds to the consensus DNA sequence 5'-(A/T)TTAATGA-3'. In oligodendrocytes, binds to MBP and PLP1 promoter regions

LOCALIZAÇÃO

Nucleus

VIAS BIOLÓGICAS (5)
Regulation of gene expression in early pancreatic precursor cellsRegulation of gene expression in beta cellsDevelopmental Lineage of Multipotent Pancreatic Progenitor CellsDevelopmental Lineage of Pancreatic Ductal CellsDevelopmental Lineage of Pancreatic Acinar Cells
MECANISMO DE DOENÇA

Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy

An autosomal recessive neurodegenerative disorder characterized by early-onset hypotonia which progresses to a pyramidal syndrome with ataxia, spasticity, hyperreflexia, weakness and loss of ambulation. Brain imaging shows cerebellar atrophy and hypomyelinating leukodystrophy.

EXPRESSÃO TECIDUAL(Tecido-específico)
Brain Spinal cord cervical c-1
147.1 TPM
Substância negra
53.3 TPM
Hipocampo
43.3 TPM
Brain Putamen basal ganglia
30.9 TPM
Hipotálamo
26.2 TPM
OUTRAS DOENÇAS (1)
spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy
HGNC:19321UniProt:Q9C056

Variantes genéticas (ClinVar)

232 variantes patogênicas registradas no ClinVar.

🧬 GLRX5: NM_016417.3(GLRX5):c.268G>A (p.Val90Met) ()
🧬 GLRX5: NM_016417.3(GLRX5):c.336del (p.Tyr113fs) ()
🧬 GLRX5: NM_016417.3(GLRX5):c.367G>C (p.Asp123His) ()
🧬 GLRX5: NM_016417.3(GLRX5):c.80C>G (p.Pro27Arg) ()
🧬 GLRX5: GRCh37/hg19 14q31.1-32.2(chr14:79886061-96870809)x1 ()
Ver todas no ClinVar

Classificação de variantes (ClinVar)

Distribuição de 2,424 variantes classificadas pelo ClinVar.

485
1939
VUS (20.0%)
Benigna (80.0%)
VARIANTES MAIS SIGNIFICATIVAS
KIF1C: NM_006612.6(KIF1C):c.1694G>A (p.Gly565Glu) [Uncertain significance]
KIF1C: NM_006612.6(KIF1C):c.1049G>A (p.Cys350Tyr) [Uncertain significance]
KIF1C: NM_006612.6(KIF1C):c.1573G>T (p.Val525Phe) [Uncertain significance]
KIF1C: NM_006612.6(KIF1C):c.393T>G (p.Ser131Arg) [Uncertain significance]
KIF1C: NM_006612.6(KIF1C):c.219G>A (p.Val73=) [Likely benign]

Diagnóstico

Os sinais que médicos procuram e os exames que confirmam

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Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Pipeline de tratamentos
Pipeline regulatório — de medicamentos já aprovados a drogas em pesquisa exploratória.
·Pré-clínico5
Medicamentos catalogadosEnsaios clínicos· 0 medicamentos · 5 ensaios
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Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Ataxia espástica

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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

🟢 Recrutando agora

2 pesquisas recrutando participantes. Converse com seu médico sobre a possibilidade de participar.

Outros ensaios clínicos

6 ensaios clínicos encontrados, 2 ativos.

Distribuição por fase
Ver todos no ClinicalTrials.gov
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Publicações mais relevantes

🥉Melhor nível de evidência: Relato de caso
Timeline de publicações
364 papers (10 anos)
#1

Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxia.

Nature communications2026 Feb 14

Most patients with a rare movement disorder (MD) do not receive a molecular diagnosis, and the underlying genetic variants and mediating genes remain elusive. Here, we evaluate the diagnostic accuracy of conventional and next-generation sequencing-based genetic testing strategies in a cohort of 2,811 individuals with ataxia, spastic paraplegia and dystonia. Exome sequencing establishes genetic diagnoses in 19.3% of cases, and specificity of phenotypic features and age at testing are positive predictors. Genome analysis 'beyond the exome' increases the diagnostic yield by 7.5%, mostly due to the improved detection of structural variants and repeat expansions. Unsolved cases are included in the Solve-RD cohort and subjected to gene-burden analysis, providing evidence for loss-of-function variants in X-chromosomal CD99L2 causing spastic ataxia. Cellular studies show that the transmembrane protein CD99L2 occurs mainly in a ubiquitinated form and serves as an activating interactor of the calcium-dependent protease CAPN1. Ablation of cytoplasmic or extracellular domains of CD99L2 leads to its intracellular mislocalization and abrogation of its interplay with CAPN1. Transcriptome analysis in CD99L2 patient-derived fibroblasts reveals synaptic function-specific disturbances. Impaired CAPN1 activation and dysregulation of downstream neuronal pathways constitute the likely molecular cause for neurodegeneration.

#2

Missense variants in TUBA4A cause myo-tubulinopathies.

Brain : a journal of neurology2026 Feb 12

Tubulinopathies encompass a spectrum of disorders resulting from variants in genes encoding α- and β-tubulins, the key components of microtubules. While previous studies have linked de novo or dominantly inherited TUBA4A missense variants to neurodegenerative phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, spastic ataxia, and recently, an isolated congenital myopathy, the full phenotypic and genotypic spectrum of TUBA4A-related disorders remains incompletely characterised. In this multi-centre study, we identified one previously reported and 12 novel TUBA4A missense variants in 31 individuals from 19 unrelated families. Remarkably, individuals in 17 families presented with a myopathy without any CNS involvement or history of such disease. In the remaining two families, we observed probands with cerebellar ataxia and epilepsy accompanying proximal and axial muscle weakness along with protein aggregation. The coexistence of neuromuscular and neurodegenerative features with protein aggregation defines a multisystem proteinopathy. These two families thus establish the first association between TUBA4A and multisystem proteinopathy. Our cohort exhibited diverse genotypes and inheritance patterns: four families demonstrated autosomal dominant transmission through heterozygous variants in TUBA4A, three probands had recessive inheritance due to homozygous variants, while the respective heterozygous carriers were asymptomatic; five probands carried de novo variants, and nine probands with heterozygous variants were classified as sporadic cases. Clinical phenotypes ranged from mild to severe myopathy, predominantly affecting the axial and paraspinal muscles. We observed a range of disease onset, from congenital to late adulthood. Creatine kinase levels were variable, ranging from normal to highly elevated. Cardiac function remained preserved across the cohort. Muscle biopsies showed heterogenous myopathic changes, including myofibre size variation, nemaline bodies, core-like regions, and internal nuclei. Immunohistochemical analysis revealed protein accumulations positive for TDP-43 (n=2), p62 (n=5), and TUBA4A (n=6). Complementary in silico and in vitro investigations suggested that the identified TUBA4A variants cause significant protein abnormalities and may differentially impact microtubule dynamics. Correlation analyses integrating clinical severity, variant location, and mechanistic readouts further demonstrated that domain specificity within TUBA4A influences both the pattern of muscle involvement and the extent of microtubule disruption. Our findings establish myo-tubulinopathies as distinct clinical entities, encompassing both primary myopathies and multisystem proteinopathies with muscle involvement. This study broadens the phenotypic and genotypic spectrum of TUBA4A-related disorders beyond autosomal dominant or de novo mechanisms and neurodegenerative presentations. These results underscore the importance of considering TUBA4A variants in the differential diagnosis of axial myopathies and multisystem proteinopathies, regardless of central nervous system (CNS) involvement.

#3

Generation of eight human induced pluripotent stem cells lines from patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS).

Stem cell research2026 Mar

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a rare inherited neurodegenerative disorder causing progressive spasticity, ataxia and peripheral neuropathy, leading to significant motor and sensory impairments. To advance the study of ARSACS pathogenesis and therapeutic development, we generated eight induced pluripotent stem cell (iPSC) lines from patient-derived fibroblasts or peripheral blood mononuclear cells (PBMCs) using non-integrating Sendai virus-based reprogramming method and covering four different SACS gene mutations. These iPSC lines provide a powerful platform to investigate disease mechanisms, evaluate therapeutic candidates, and support the development of personalized medicine approaches for ARSACS. The phenotypic spectrum of SPG7-related neurologic disorder includes uncomplicated spastic ataxia, complicated spastic ataxia, spinocerebellar ataxia, and isolated optic nerve atrophy. Although onset typically occurs in adulthood, it may start in infancy or as late as age 72 years. Initially the spastic paraplegia is typically characterized by insidiously progressive bilateral leg weakness and spasticity or cerebellar findings (ataxia, dysarthria, and dysphagia) or both. Other central nervous system findings include decreased visual acuity due to optic neuropathy, cognitive impairment, and dystonia. Peripheral nervous system involvement manifests as motor and sensory neuropathy, neuropathic pain, and amyotrophy. Associated musculoskeletal involvement includes pes cavus and scoliosis. Spasticity and ataxia are progressive and may result in wheelchair dependence. The diagnosis of SPG7-related neurologic disorder is established in a proband with suggestive findings and biallelic pathogenic variants in SPG7 identified by molecular genetic testing. Treatment of manifestations: Multidisciplinary care by specialists in neurology, ophthalmology, low vision services, audiology, urology, physiatry, occupational therapy, physical therapy, orthopedics, feeding therapy and nutrition, speech-language therapy, social work, psychology, and clinical genetics. Surveillance: Monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations with routinely scheduled evaluations by treating specialists. SPG7-related neurologic disorder is inherited in an autosomal recessive manner. (Several studies have reported a single [heterozygous] pathogenic variant in SPG7 in individuals with SPG7-related neurologic disorder suggesting the possibility of autosomal dominant inheritance; however, the possibility of autosomal dominant inheritance remains controversial.) If both parents are known to be heterozygous for an SPG7 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants. Once the SPG7 pathogenic variants have been identified in an affected family member, heterozygote testing for at-risk relatives and prenatal/preimplantation genetic testing for SPG7-related neurologic disorder are possible.

#4

Mild and late onset forms of type I 3-methylglutaconic aciduria presenting as isolated cerebellar ataxia without leukodystrophy: case reports and phenotype expansion.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2026 Jan 02

Type I 3-Methylglutaconic Aciduria (MGCA1) is a metabolic disorder inherited in an autosomal recessive manner. It is caused by a deficiency in the 3-methylglutaconyl-CoA hydratase encoded by the AUH gene, leading to abnormal excretion of urinary organic acids. While the pediatric phenotype encompasses a spectrum ranging from isolated developmental delay to severe forms with leukodystrophy, developmental delay, spastic tetraplegia and movement disorders, the adult phenotype corresponds to a leukodystrophy with spastic ataxia, progressive dementia, and optic neuropathy. Due to its rarity, MGCA1 is most likely underdiagnosed, or diagnosed with an important delay, leading to inadequate care or genetic counselling. A better understanding of the disease's phenotype is thus required to facilitate its clinical and genetic diagnosis, in turn favoring clinical care and genetic counselling. We report two new MGCA1 patients, including an adult male patient with pure, late-onset, and progressive cerebellar ataxia, without optic neuropathy or leukodystrophy. A young female patient case is also reported with moderate developmental delay and leukodystrophy, offering 14-year follow-up data under carnitine supplementation. In both cases, urinary organic acid chromatography was critical to the diagnostic process by demonstrating abnormal and specific urinary organic acids excretion. The description of new, mild and/or late-onset phenotypes expands the clinical and radiological spectrum of MGCA1. Our results show that late-onset MGCA1 patients may present with pure cerebellar ataxia without leukodystrophy, contrasting with current knowledge. These results support the fact that AUH should always be sequenced in patients with pure cerebellar ataxia, but also that urinary organic acid chromatography being a simple, rapid, and cost-effective test, should be performed as a first-tier analysis in all patients with unresolved neurological symptoms. The importance of identifying MGCA1 patients is reinforced by the possibility of implementing a low-risk and possibly effective therapy with low-protein diet and L-carnitine supplementation.

#5

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay in Two Half-Siblings.

Annals of clinical and translational neurology2026 Feb

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by biallelic pathogenic variants in the SACS gene. We report the clinical, radiologic and neurophysiologic features of a pair of half-siblings who presented with progressive cerebellar ataxia, peripheral neuropathy and upper motor neuron signs. After significant diagnostic delay, genetic testing revealed both harboured a shared, paternally inherited microdeletion encompassing the SACS gene, and each harboured a different single nucleotide variant in SACS, each likely maternally inherited. Recognition of the clinical and radiologic phenotype of ARSACS may facilitate early diagnosis of this disorder even in the face of uncommon inheritance patterns.

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Functional Network Profiles in ARSACS Disclosed by Aptamer-Based Proteomic Technology.

Frontiers in neurology
2021

A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
2021

Wiedemann-Rautenstrauch syndrome in an Indian patient with biallelic pathogenic variants in POLR3A.

American journal of medical genetics. Part A
2021

Two intronic cis-acting variants in both alleles of the POLR3A gene cause progressive spastic ataxia with hypodontia.

Clinical genetics
2021

Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations.

Neurogenetics
2020

Case Report: Expanding the Genetic and Phenotypic Spectrum of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

Frontiers in genetics
2021

Two cases of early-onset autosomal recessive spastic ataxia of Charlevoix-Saguenay diagnosed in adulthood.

Clinical neurology and neurosurgery
2023

Wheelchair mobility, motor performance and participation of adult wheelchair users with ARSACS: a cross-sectional study.

Disability and rehabilitation. Assistive technology
2021

SPG46 due to truncating mutations in GBA2: Two cases from India.

Parkinsonism & related disorders
2021

A novel PNPLA6 mutation in a Turkish family with intractable Holmes tremor and spastic ataxia.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
2020

Clinical Features and Molecular Genetics of Autosomal Recessive Ataxia in the Turkish Population.

Journal of pediatric neurosciences
Ver todos os 255 no EuropePMC

Associações

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Comunidades

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Doenças relacionadas

Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico

Ordenadas pelo número de sintomas em comum.

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.

  1. Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxia.
    Nature communications· 2026· PMID 41690933mais citado
  2. Missense variants in TUBA4A cause myo-tubulinopathies.
    Brain : a journal of neurology· 2026· PMID 41678358mais citado
  3. Generation of eight human induced pluripotent stem cells lines from patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS).
    Stem cell research· 2026· PMID 41529449mais citado
  4. Mild and late onset forms of type I 3-methylglutaconic aciduria presenting as isolated cerebellar ataxia without leukodystrophy: case reports and phenotype expansion.
    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology· 2026· PMID 41483232mais citado
  5. Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay in Two Half-Siblings.
    Annals of clinical and translational neurology· 2026· PMID 41353788mais citado
  6. Novel heterozygous UCHL1 variant causing severe optic atrophy and vision loss.
    Ophthalmic Genet· 2026· PMID 41958053recente
  7. Six novel SACS mutations expand the autosomal recessive spastic ataxia of Charlevoix-Saguenay spectrum.
    Orphanet J Rare Dis· 2026· PMID 41923236recente
  8. A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation in Tuba4a.
    bioRxiv· 2026· PMID 41889878recente
  9. Expanding the AFG3L2 Spectrum: A Link to Axonal Neuropathy.
    Neurol Genet· 2026· PMID 41883704recente
  10. Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders.
    BMC Med· 2026· PMID 41877227recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:316226(Orphanet)
  2. MONDO:0017845(MONDO)
  3. GARD:21401(GARD (NIH))
  4. Variantes catalogadas(ClinVar)
  5. Busca completa no PubMed(PubMed)
  6. Q21082498(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

Ataxia espástica
Compêndio · Raras BR

Ataxia espástica

ORPHA:316226 · MONDO:0017845
CID-10
G11.4 · Paraplegia espástica hereditária
Ensaios
2 ativos
MedGen
UMLS
C1849156
EuropePMC
Wikidata
Papers 10a
Evidência
🥉 Relato de caso
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