# Neurodegenerescência com acúmulo cerebral de ferro

> Página oficial: https://raras.org/doenca/neurodegenerescencia-com-acumulo-cerebral-de-ferro
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 385 — https://www.orpha.net/en/disease/detail/385
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A neurodegeneração com acumulação cerebral de ferro (NBIA, antigamente síndrome de Hallervorden-Spatz) abrange um grupo de doenças neurodegenerativas raras caracterizadas por disfunção extrapiramidal progressiva (distonia, rigidez, coreoatetose), acumulação de ferro no cérebro e presença de esferóides axonais, geralmente limitados ao sistema nervoso central.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 1 000 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, X-linked dominant

## Sinais e sintomas (388 fenótipos HPO)

- **Leucodistrofia** — HPO: HP:0002415
- **Infertilidade** — HPO: HP:0000789
- **Amenorreia primária** — HPO: HP:0000786
- **Diabetes mellitus tipo 1** — HPO: HP:0100651
- **Azoospermia** — HPO: HP:0000027
- **Opistótono** — HPO: HP:0002179
- **Perda de peso** — HPO: HP:0001824
- **Retinopatia** — HPO: HP:0000488
- **Irritabilidade** — HPO: HP:0000737
- **Tosse** — HPO: HP:0012735
- **Comportamento violento** — HPO: HP:0008760
- **Palidez do disco óptico** — HPO: HP:0000543
- **Anormalidade da língua** — HPO: HP:0000157
- **Atrofia da língua** — HPO: HP:0012473
- **Rigidez muscular** — HPO: HP:0003552
- **Aumento da suscetibilidade a fraturas** — HPO: HP:0002659
- **Incapacidade de andar** — HPO: HP:0002540
- **Postura anormal** — HPO: HP:0002533
- **Inércia** — HPO: HP:0030216
- **Alucinações visuais** — HPO: HP:0002367
- **Anormalidade no teste de visão de cores** — HPO: HP:0030584
- **Quadriplegia espástica progressiva** — HPO: HP:0002478
- **Atrofia da medula espinhal** — HPO: HP:0006827
- **Nistagmo horizontal** — HPO: HP:0000666
- **Ataxia da marcha progressiva** — HPO: HP:0007240
- **Reflexo patelar hiperativo** — HPO: HP:0007083
- **Confusão** — HPO: HP:0001289
- **Afasia motora** — HPO: HP:0002427
- **Crise tônico-clônica bilateral** — HPO: HP:0002069
- **Letargia** — HPO: HP:0001254
- **Febre** — HPO: HP:0001945
- **Morfologia anormal do pé** — HPO: HP:0001760
- **Paraplegia espástica progressiva** — HPO: HP:0007020
- **Quedas** — HPO: HP:0002527
- **Distonia lingual** — HPO: HP:0031008
- **Postura curvada** — HPO: HP:0025403
- **Disfunção do neurônio motor superior** — HPO: HP:0002493
- **Anormalidade do dedo** — HPO: HP:0001167
- **Transtorno afetivo bipolar** — HPO: HP:0007302
- **Anormalidade da função mental superior** — HPO: HP:0011446
- _...e mais 348 sintomas. Ver https://raras.org/doenca/neurodegenerescencia-com-acumulo-cerebral-de-ferro._

## Genes associados (14)

- **FTL** — Ferritin light chain [Disease-causing germline mutation(s) in]
  - Função: Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role
- **FA2H** — Fatty acid 2-hydroxylase [Candidate gene tested in]
  - Função: Catalyzes the hydroxylation of free fatty acids at the C-2 position to produce 2-hydroxy fatty acids, which are building blocks of sphingolipids and glycosphingolipids common in neural tissue and epid
- **TBCE** — Tubulin-specific chaperone E [Candidate gene tested in]
  - Função: Tubulin-folding protein; involved in the second step of the tubulin folding pathway and in the regulation of tubulin heterodimer dissociation. Required for correct organization of microtubule cytoskel
- **ATP13A2** — Polyamine-transporting ATPase 13A2 [Disease-causing germline mutation(s) in]
  - Função: ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine (PubMed:31996848). Also stimulates cellular uptake of polyamines and protects against polyamine toxicity (PubMed:319
- **CRAT** — Carnitine O-acetyltransferase [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the reversible transfer of acyl groups from carnitine to coenzyme A (CoA) and regulates the acyl-CoA/CoA ratio. Also plays a crucial role in the transport of fatty acids for beta-oxidation (
- **CP** — Ceruloplasmin [Disease-causing germline mutation(s) in]
  - Função: Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron tran
- **REPS1** — RalBP1-associated Eps domain-containing protein 1 [Disease-causing germline mutation(s) in]
  - Função: May coordinate the cellular actions of activated EGF receptors and Ral-GTPases
- **C19orf12** — Protein C19orf12 [Disease-causing germline mutation(s) in]
- **DCAF17** — DDB1- and CUL4-associated factor 17 [Disease-causing germline mutation(s) in]
  - Função: May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex
- **WDR45** — WD repeat domain phosphoinositide-interacting protein 4 [Disease-causing germline mutation(s) in]
  - Função: Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradatio
- **PLA2G6** — 85/88 kDa calcium-independent phospholipase A2 [Disease-causing germline mutation(s) in]
  - Função: Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. Hydrolyzes the ester bond of
- **FTH1** — Ferritin heavy chain [Disease-causing germline mutation(s) in]
  - Função: Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hyd
- **PANK2** — Pantothenate kinase 2, mitochondrial [Disease-causing germline mutation(s) in]
  - Função: Mitochondrial isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis (PubMed:15659606, PubMe
- **COASY** — Bifunctional coenzyme A synthase [Disease-causing germline mutation(s) in]
  - Função: Bifunctional enzyme that catalyzes the fourth step of the coenzyme A biosynthetic pathway, the adenylation of 4'-phosphopantetheine, and the fifth step, the phosphorylation of dephospho-CoA to CoA

## Ensaios clínicos ativos (2)

- **NCT05522374** [RECRUITING]: TIRCON International NBIA Registry — https://clinicaltrials.gov/study/NCT05522374
- **NCT06596746** [RECRUITING]: Neurodegenerative Diseases Progression Markers (MARKERS-NDD) — https://clinicaltrials.gov/study/NCT06596746
- **NCT05696912** [UNKNOWN]: Functional Tests to Resolve Unsolved Rare Diseases. Rares. — https://clinicaltrials.gov/study/NCT05696912
- **NCT05615571** [COMPLETED]: Testing of NBIA Genes: Analysis of Genetic Heterogeneity and Validation of Mitochondrial Markers for Assessing Causality of Sequence Variants. — https://clinicaltrials.gov/study/NCT05615571
- **NCT02587858** [UNKNOWN]: NBIAready: Online Collection of Natural History Patient-reported Outcome Measures — https://clinicaltrials.gov/study/NCT02587858
- **NCT03572114** [UNKNOWN]: Imaging Neuromelanin and Iron in Dystonia/Parkinsonism — https://clinicaltrials.gov/study/NCT03572114

## Doenças relacionadas (por similaridade fenotípica)

- [NÃO RARA NA EUROPA: Doença de Parkinson](https://raras.org/doenca/nao-rara-na-europa-doenca-de-parkinson) — ORPHA:319705 — 133 sintomas em comum
- [Neurodegenerescência associada a PLA2G6](https://raras.org/doenca/neurodegenerescencia-associada-a-pla2g6) — ORPHA:329303 — 127 sintomas em comum
- [Neurodegenerescência associada a pantotenato quinase](https://raras.org/doenca/neurodegenerescencia-associada-a-pantotenato-quinase) — ORPHA:157850 — 114 sintomas em comum
- [Alteração do metabolismo e transporte de ferro](https://raras.org/doenca/alteracao-do-metabolismo-e-transporte-de-ferro) — ORPHA:309842 — 104 sintomas em comum
- [Ataxia espástica](https://raras.org/doenca/ataxia-espastica) — ORPHA:316226 — 102 sintomas em comum
- [Síndrome distonia-plus](https://raras.org/doenca/sindrome-distonia-plus) — ORPHA:98203 — 101 sintomas em comum
- [Doença de Parkinson de início juvenil](https://raras.org/doenca/doenca-de-parkinson-de-inicio-juvenil) — ORPHA:2828 — 99 sintomas em comum
- [Lipofuscinose ceroide neuronal](https://raras.org/doenca/lipofuscinose-ceroide-neuronal) — ORPHA:216 — 82 sintomas em comum
- [Epilepsia, mioclonia progressiva](https://raras.org/doenca/epilepsia-mioclonia-progressiva) — ORPHA:98261 — 81 sintomas em comum
- [Ataxia cerebelosa ligada ao X](https://raras.org/doenca/ataxia-cerebelosa-ligada-ao-x) — ORPHA:247765 — 79 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

---

**Citação sugerida**: Raras.org — Neurodegenerescência com acúmulo cerebral de ferro. Disponível em: https://raras.org/doenca/neurodegenerescencia-com-acumulo-cerebral-de-ferro
**Formato HTML**: https://raras.org/doenca/neurodegenerescencia-com-acumulo-cerebral-de-ferro
**Formato RDF/Turtle**: https://raras.org/api/rdf?orpha=385