A MPAN (Neurodegeneração Associada à Proteína da Membrana Mitocondrial), também conhecida como Neurodegeneração com Acúmulo de Ferro no Cérebro (NBIA) devido a mutações no gene C19orf12, é uma doença neurológica degenerativa autossômica recessiva. Isso significa que a pessoa precisa herdar uma cópia do gene alterado de cada um dos pais para desenvolver a condição. A MPAN é caracterizada pelo acúmulo de ferro em regiões específicas do cérebro, geralmente nos gânglios da base (áreas importantes para o controle do movimento). Ela está associada a sintomas que pioram lentamente, como rigidez muscular (espasticidade) e movimentos involuntários ou posturas anormais (distonia). Também causa problemas nos nervos que controlam os músculos (neuropatia motora axonal), perda progressiva da visão (atrofia do nervo óptico), perda de memória e dificuldade de raciocínio (declínio cognitivo), além de alterações psiquiátricas e de comportamento.
Introdução
O que você precisa saber de cara
A MPAN (Neurodegeneração Associada à Proteína da Membrana Mitocondrial), também conhecida como Neurodegeneração com Acúmulo de Ferro no Cérebro (NBIA) devido a mutações no gene C19orf12, é uma doença neurológica degenerativa autossômica recessiva. Isso significa que a pessoa precisa herdar uma cópia do gene alterado de cada um dos pais para desenvolver a condição. A MPAN é caracterizada pelo acúmulo de ferro em regiões específicas do cérebro, geralmente nos gânglios da base (áreas importantes para o controle do movimento). Ela está associada a sintomas que pioram lentamente, como rigidez muscular (espasticidade) e movimentos involuntários ou posturas anormais (distonia). Também causa problemas nos nervos que controlam os músculos (neuropatia motora axonal), perda progressiva da visão (atrofia do nervo óptico), perda de memória e dificuldade de raciocínio (declínio cognitivo), além de alterações psiquiátricas e de comportamento.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
Encontrou um erro ou informação desatualizada? Sugira uma correção →
Entender a doença
Do básico ao detalhe, leia no seu ritmo
Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 30 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 58 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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
2 genes identificados com associação a esta condição. Padrão de herança: Autosomal recessive.
MitochondrionMitochondrion membraneEndoplasmic reticulumCytoplasm, cytosol
Neurodegeneration with brain iron accumulation 4
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA4 results in speech difficulty, extrapyramidal signs, oromandibular and generalized dystonia, and parkinsonism. Most patients have progressive involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor plantar responses.
MitochondrionMitochondrion membraneEndoplasmic reticulumCytoplasm, cytosol
Neurodegeneration with brain iron accumulation 4
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA4 results in speech difficulty, extrapyramidal signs, oromandibular and generalized dystonia, and parkinsonism. Most patients have progressive involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor plantar responses.
Variantes genéticas (ClinVar)
144 variantes patogênicas registradas no ClinVar.
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 — Neurodegenerescência associada a proteína de membrana mitocondrial
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
Ensaios em destaque
🟢 Recrutando agora
1 pesquisa recrutando participantes. Converse com seu médico sobre a possibilidade de participar.
Outros ensaios clínicos
Publicações mais relevantes
Inflammation and oligoclonal bands in cerebrospinal fluid in neurodegeneration associated with C19orf12 mutations.
Analysis of cerebrospinal fluid examination can provide valuable information about the ongoing pathological processes in the central nervous system. To demonstrate chronic inflammation, oligoclonal bands (OCB) are detected and are typical of chronic demyelinating disease-multiple sclerosis (MS). This study aimed to detect OCB and white matter hyperintensities in patients with C19orf12 mutations. Thirteen patients with C19orf12 mutations causing mitochondrial membrane protein-associated neurodegeneration (MPAN) were examined. Eight patients exhibited oligoclonal bands, with 6 having type 3 and 2 having type 2. All patients with OCB and 3 without OCB showed myelin loss. Our findings, which reveal chronic inflammation in NBIA-MPAN alongside myelin loss, provide new insights into disease pathology and promote discussion of anti-inflammatory treatments in C19orf12 carriers.
Autophagy-related proteomics reveals lysosomal alterations linked to C19orf12 mutations and candidate biomarkers in MPAN patients' fibroblasts.
Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) is the third most common genetically-defined subtype of Neurodegeneration with Brain Iron Accumulation (NBIA), a group of rare, clinically heterogeneous disorders. The MPAN pathomechanism, including the link between C19orf12 mutations, iron accumulation, and metabolic alterations, is still poorly understood. While earlier research pointed to impaired autophagy in MPAN, a comprehensive understanding remains elusive. Here, we investigated the autophagy-linked proteome in primary fibroblasts derived from 18 MPAN patients and identified distinct alterations in autophagy-related protein expression. Importantly, a subset of these proteomic changes showed significant associations with disease severity, highlighting their potential relevance as biomarkers of clinical progression. Functional analyses further revealed increased lysosomal acidification as the most consistently affected autophagy-related process in MPAN fibroblasts. Notably, both proteomic and functional alterations were associated with C19orf12 mutation zygosity, underscoring its modulatory role in disease-relevant cellular pathways.
Distinct Neurodegenerative Pathways in Two NBIA Subtypes: Inflammatory Activation in C19orf12 but Not in PANK2 Mutation Carriers.
Biomarker analysis in neurodegeneration with brain iron accumulation (NBIA) can offer valuable insights into the disease's pathology and natural history. Twenty-five patients with C19orf12 mutations causing mitochondrial membrane protein-associated neurodegeneration (MPAN), 12 patients with PANK2 mutations causing pantothenate kinase-associated neurodegeneration (PKAN), and 30 age- and gender-matched controls were studied. Serum levels of MMP-9, S100B, ICAM-1, E- and P-selectins, total α-synuclein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Tau, ubiquitin-C-terminal hydrolase-L1 (UCH-L1), and brain-derived neurotrophic factor (BDNF) were measured. Clinical status was evaluated with dedicated rating scales. Compared to the control group, MPAN patients had significantly higher serum levels of nearly all biomarkers, except BDNF. NfL, GFAP, and UCH-L1, were elevated by 5, 2, and 3.5 times, respectively. PKAN patients showed no significant differences in GFAP, UCH-L1, and S100B levels compared to controls. However, NfL and Tau levels were increased by 3 and 1.8 times, respectively. A correlation was observed between disease severity and levels of NfL, Tau, and UCH-L1 in MPAN, and GFAP, Tau, and UCH-L1 in PKAN. Patients with MPAN and PKAN showed increased levels of neurodegeneration biomarkers. Elevated inflammation and blood-brain barrier dysfunction biomarkers were specific to MPAN patients.
An Update and Perspectives on Mitochondrial Membrane Protein-Associated Neurodegeneration and C19orf12 Research.
Mitochondrial Membrane Protein-Associated Neurodegeneration is a rare monogenic form of neurodegeneration characterized by iron accumulation in the brain. It is due to variants in the orphan gene C19orf12. Since its definition in 2011, many scientific groups have investigated the clinical features and molecular underpinnings of the disorder. In this review, we summarize the main points of progress in this field, trying to highlight the issues that need further attention and efforts to speed up the diagnostic path, improve the existing treatment options, and define targeted therapies.
Novel Variant in C19orf12 Gene Causing Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) - Case Report and a Brief Review of Indian Literature on MPAN.
The purpose of this overview is to: 1.. Briefly describe the clinical characteristics of neurodegeneration with brain iron accumulation (NBIA); 2.. Review the genetic causes of NBIA; 3.. Review the differential diagnosis of NBIA with a focus on genetic conditions; 4.. Provide an evaluation strategy to identify the genetic cause of NBIA in a proband (when possible); 5.. Review high-level management of NBIA; 6.. Inform genetic counseling of family members of an individual with NBIA.
Publicações recentes
Neuropathologic Characterisation of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) With Coexisting α-Synuclein and Tau Pathology in a Young Adult.
Phase separation of C19orf12 regulates BNIP3 protein quality control and maintains neuronal mitophagy.
Inflammation and oligoclonal bands in cerebrospinal fluid in neurodegeneration associated with C19orf12 mutations.
Autophagy-related proteomics reveals lysosomal alterations linked to C19orf12 mutations and candidate biomarkers in MPAN patients' fibroblasts.
Neurodegeneration With Brain Iron Accumulation and Ferroptosis Disorders in Children and Adults: An Imaging Review.
📚 EuropePMC42 artigos no totalmostrando 74
Inflammation and oligoclonal bands in cerebrospinal fluid in neurodegeneration associated with C19orf12 mutations.
Parkinsonism & related disordersAutophagy-related proteomics reveals lysosomal alterations linked to C19orf12 mutations and candidate biomarkers in MPAN patients' fibroblasts.
Neurobiology of diseaseNeurodegeneration With Brain Iron Accumulation and Ferroptosis Disorders in Children and Adults: An Imaging Review.
Journal of neuroimaging : official journal of the American Society of NeuroimagingDistinct Neurodegenerative Pathways in Two NBIA Subtypes: Inflammatory Activation in C19orf12 but Not in PANK2 Mutation Carriers.
CellsPatient-Derived Neurons Exhibit α-Synuclein Pathology and Previously Unrecognized Major Histocompatibility Complex Class I Elevation in Mitochondrial Membrane Protein-Associated Neurodegeneration.
Movement disorders : official journal of the Movement Disorder SocietyAn Update and Perspectives on Mitochondrial Membrane Protein-Associated Neurodegeneration and C19orf12 Research.
Brain sciencesNeurodegeneration with Brain Iron Accumulation.
Advances in experimental medicine and biologyNovel Variant in C19orf12 Gene Causing Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) - Case Report and a Brief Review of Indian Literature on MPAN.
Annals of Indian Academy of NeurologyC19orf12 gene variants causing mitochondrial membrane protein-associated neurodegeneration (MPAN).
European journal of human genetics : EJHGGeneration of four human induced pluripotent stem cell lines derived from patients with MPAN, subtype of NBIA, carrying the c.204_214del11 mutation in the C19orf12 gene.
Stem cell researchMetabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA).
Biochimica et biophysica acta. Molecular basis of diseaseMetabolic impairments in neurodegeneration with brain iron accumulation.
Biochimica et biophysica acta. BioenergeticsMitochondrial Membrane Protein-Associated Neurodegeneration with Brain Iron Accumulation: Diagnosis by MRI.
Neurology IndiaGenetic Targets and Applications of Iron Chelators for Neurodegeneration with Brain Iron Accumulation.
ACS bio & med chem AuTeaching NeuroImage: Mitochondrial Membrane Protein-Associated Neurodegeneration: An MRI Pattern Recognition.
NeurologyMitochondrial-Membrane-Protein-Associated Neurodegeneration in Longitudinal Magnetic Resonance Imaging Over 11 Years of Follow-Up.
Journal of clinical neurology (Seoul, Korea)Estimation of Ambulation and Survival in Neurodegeneration with Brain Iron Accumulation Disorders.
Movement disorders clinical practice'Comb Sign': A Novel Appearance of Substantia Nigra in Mitochondrial Membrane Protein-Associated Neurodegeneration.
Annals of Indian Academy of NeurologyRehabilitation for Mitochondrial Membrane Protein-Related Neurodegeneration: A Case Study.
CureusPhenotype and natural history of mitochondrial membrane protein-associated neurodegeneration.
Brain : a journal of neurologyGeneration of two human iPSC lines, HMGUi004-A and FINCBi004-A, from fibroblasts of MPAN patients carrying pathogenic recessive mutations in the gene C19orf12.
Stem cell researchOlfactory status in neurodegeneration with brain iron accumulation disorders.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyAutosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late-Onset Phenotypes.
Movement disorders : official journal of the Movement Disorder SocietyA novel C19ORF12 mutation in two MPAN sisters treated with deferiprone.
BMC neurologyMitochondrial Membrane Protein-Associated Neurodegeneration (MPAN): Two Phenotypes-Dystonia and Spastic Paraparesis.
Annals of Indian Academy of NeurologyA novel C19orf12 frameshift mutation in a MPAN pedigree impairs mitochondrial function and connectivity leading to neurodegeneration.
Parkinsonism & related disordersIdentification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro.
PharmaceuticsManic syndrome in mitochondrial membrane protein-associated neurodegeneration: A case report.
Psychiatry and clinical neurosciencesCase Report: Identification of a De novo C19orf12 Variant in a Patient With Mitochondrial Membrane Protein-Associated Neurodegeneration.
Frontiers in geneticsTwo cases with mitochondrial membrane protein-associated neurodegeneration: genetic features and long-term clinical follow-up.
NeurocaseNovel C19orf12 loss-of-function variant leading to neurodegeneration with brain iron accumulation.
NeurocaseNBIA Syndromes: A Step Forward from the Previous Knowledge.
Neurology IndiaMitochondrial Membrane Protein-associated Neurodegeneration due to Novel Homozygous Mutation in the C19orf12 Gene.
Annals of Indian Academy of NeurologyConsensus clinical management guideline for beta-propeller protein-associated neurodegeneration.
Developmental medicine and child neurologyChallenges in the approach and reporting of atypical manifestations of membrane protein-associated neurodegeneration (MPAN): An editorial.
Parkinsonism & related disordersC19orf12 mutation causing mitochondrial membrane-protein Associated Neurodegeneration masquerading as spastic paraplegia.
Parkinsonism & related disordersA De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration.
Molecular genetics & genomic medicineDistal muscle weakness and optic atrophy without central nervous system involvement in a patient with a homozygous missense mutation in the C19ORF12-gene.
Clinical neurology and neurosurgeryEmerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders.
Frontiers in neurologyMitochondrial Membrane Protein-Associated Neurodegeneration: A Case Series of Six Children.
Annals of Indian Academy of NeurologySystematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases.
Frontiers in neuroscienceRetrospective analysis of 17 patients with mitochondrial membrane protein-associated neurodegeneration diagnosed in Russia.
Parkinsonism & related disordersCardiac disease in mitochondrial membrane protein-associated neurodegeneration (MPAN) due to variants in C19orf12.
Parkinsonism & related disordersThe Downregulation of c19orf12 Negatively Affects Neuronal and Musculature Development in Zebrafish Embryos.
Frontiers in cell and developmental biologyDominant mitochondrial membrane protein-associated neurodegeneration (MPAN) variants cluster within a specific C19orf12 isoform.
Parkinsonism & related disordersNovel dominant MPAN family with a complex genetic architecture as a basis for phenotypic variability.
Neurology. GeneticsReprogramming of a human induced pluripotent stem cell (iPSC) line from a patient with neurodegeneration with brain iron accumulation (NBIA) harboring a novel frameshift mutation in C19orf12 gene.
Stem cell researchIs there heart disease in cases of neurodegeneration associated with mutations in C19orf12?
Parkinsonism & related disordersLate-Onset Mitochondrial Membrane Protein-Associated Neurodegeneration With Extensive Brain Iron Deposition.
Movement disorders clinical practiceClinical and genetic spectrum of an orphan disease MPAN: a series with new variants and a novel phenotype.
Neurologia i neurochirurgia polskaA Novel Mutation in Neurodegeneration with Brain Iron Accumulation - A Case Report.
Neurology India[Pedigree analysis of C19ORF12 p.Asp18Tyr mutation in a family with mitochondrial membrane protein associated neurodegeneration].
Zhonghua yi xue za zhiBrain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration.
Movement disorders : official journal of the Movement Disorder SocietyAutosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN).
Molecular genetics & genomic medicineLevodopa-induced dyskinesias in mitochondrial membrane protein-associated neurodegeneration.
Neurology. Clinical practiceMitochondrial Membrane Protein Associated Neurodegeneration (MPAN) with a Novel C19orf12 Mutation in the First Decade of Life.
Indian journal of pediatricsMitochondrial membrane protein-associated neurodegeneration: a case report and literature review.
NeurocaseMitochondrial membrane protein-associated neurodegeneration.
Parkinsonism & related disordersTranscranial Sonography in Mitochondrial Membrane Protein-Associated Neurodegeneration.
Clinical neuroradiologyThe p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN.
Parkinsonism & related disordersEvolution and novel radiological changes of neurodegeneration associated with mutations in C19orf12.
Parkinsonism & related disordersA Novel Deletion Mutation of Exon 2 of the C19orf12 Gene in an Omani Family with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN).
Oman medical journalMitochondrial membrane protein-associated neurodegeneration in a Turkish patient.
Journal of pediatric neurosciencesClinical and imaging characteristics of late onset mitochondrial membrane protein-associated neurodegeneration (MPAN).
NeurocaseRetinal and optic nerve abnormalities in neurodegeneration associated with mutations in C19orf12 (MPAN).
Journal of the neurological sciencesMitochondrial Membrane Protein-Associated Neurodegeneration Mimicking Juvenile Amyotrophic Lateral Sclerosis.
Pediatric neurologyA diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging.
Arquivos de neuro-psiquiatriaMovement disorders in mitochondrial diseases.
Revue neurologique"Eye of tiger sign" mimic in an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN).
Brain & developmentBehr syndrome with homozygous C19ORF12 mutation.
Journal of the neurological sciencesC19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation.
Parkinsonism & related disordersEye of the tiger sign in a 23 year patient with mitochondrial membrane protein associated neurodegeneration.
Journal of the neurological sciencesAnalysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation.
Journal of the neurological sciencesBrain iron quantification by MRI in mitochondrial membrane protein-associated neurodegeneration under iron-chelating therapy.
Annals of clinical and translational neurologyAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
Ainda não temos associações cadastradas para Neurodegenerescência associada a proteína de membrana mitocondrial.
É de uma associação que acompanha esta doença? Fale com a gente →
Comunidades
Grupos ativos de quem convive com esta doença aqui no Raras
Ainda não existe comunidade no Raras para Neurodegenerescência associada a proteína de membrana mitocondrial
Pacientes, familiares e cuidadores se organizam em comunidades pra compartilhar experiências, fazer perguntas e se apoiar. Você pode ser o primeiro.
Tire suas dúvidas
Perguntas, dicas e experiências compartilhadas aqui na página
Participe da discussão
Faça login para postar dúvidas, compartilhar experiências e interagir com especialistas.
Fazer loginDoenças relacionadas
Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico
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.
- Inflammation and oligoclonal bands in cerebrospinal fluid in neurodegeneration associated with C19orf12 mutations.
- Autophagy-related proteomics reveals lysosomal alterations linked to C19orf12 mutations and candidate biomarkers in MPAN patients' fibroblasts.
- Distinct Neurodegenerative Pathways in Two NBIA Subtypes: Inflammatory Activation in C19orf12 but Not in PANK2 Mutation Carriers.
- An Update and Perspectives on Mitochondrial Membrane Protein-Associated Neurodegeneration and C19orf12 Research.
- Novel Variant in C19orf12 Gene Causing Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) - Case Report and a Brief Review of Indian Literature on MPAN.
- Neuropathologic Characterisation of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) With Coexisting α-Synuclein and Tau Pathology in a Young Adult.
- Phase separation of C19orf12 regulates BNIP3 protein quality control and maintains neuronal mitophagy.
- Neurodegeneration With Brain Iron Accumulation and Ferroptosis Disorders in Children and Adults: An Imaging Review.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:289560(Orphanet)
- OMIM OMIM:614298(OMIM)
- MONDO:0013674(MONDO)
- GARD:12569(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q32140736(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
