# Demência relacionada com lipidose cerebral

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

## Identificadores

- **ORPHA**: 98544 — https://www.orpha.net/en/disease/detail/98544
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Doença rara caracterizada por acúmulo de lipídios no cérebro, levando a perda visual progressiva, paraparesia espástica e macrocefalia. Pode apresentar fadiga, alterações na pele e no bulbo raquidiano, além de hipertensão pulmonar.

## Epidemiologia e herança


## Sinais e sintomas (368 fenótipos HPO)

- **Perda visual progressiva** — HPO: HP:0000529
- **Morfologia anormal da pele plantar do pé** — HPO: HP:0100872
- **Fadiga** — HPO: HP:0012378
- **Hipointensidade da substância branca cerebral na ressonância magnética** — HPO: HP:0007103
- **Paraparesia espástica** — HPO: HP:0002313
- **Macrocefalia progressiva** — HPO: HP:0004481
- **Hipertensão arterial pulmonar** — HPO: HP:0002092
- **Morfologia anormal do bulbo raquidiano** — HPO: HP:0011441
- **Sensação de temperatura prejudicada** — HPO: HP:0010829
- **Morfologia pulmonar anormal** — HPO: HP:0002088
- **Sinais de trato longo** — HPO: HP:0002423
- **Atraso do neurodesenvolvimento** — HPO: HP:0012758
- **Controle cefálico pobre** — HPO: HP:0002421
- **Aterosclerose prematura da artéria coronária** — HPO: HP:0005181
- **Desmielinização periférica** — HPO: HP:0011096
- **Dor óssea** — HPO: HP:0002653
- **Sinal piramidal anormal** — HPO: HP:0007256
- **Fratura por compressão vertebral** — HPO: HP:0002953
- **Concentração elevada de colestanol no LCR** — HPO: HP:6000203
- **Tálamo hipointenso em T2** — HPO: HP:0012690
- **Perda prematura de dentes** — HPO: HP:0006480
- **Esplenomegalia** — HPO: HP:0001744
- **Aumento do lipopigmento autofluorescente neuronal** — HPO: HP:0002074
- **Transtorno de personalidade** — HPO: HP:0012075
- **Tetraplegia espástica** — HPO: HP:0002510
- **Anormalidade dos potenciais evocados somatossensoriais centrais** — HPO: HP:0100291
- **Anormalidade morfológica do trato corticoespinhal** — HPO: HP:0002492
- **Acúmulo intracelular retilíneo de material de armazenamento de lipopigmento autofluorescente** — HPO: HP:0003226
- **Linfócitos vacuolizados** — HPO: HP:0001922
- **Infiltrados pulmonares** — HPO: HP:0002113
- **Desmielinização do SNC** — HPO: HP:0007305
- **Aumento do lipopigmento autofluorescente extraneuronal** — HPO: HP:0003463
- **Quedas frequentes** — HPO: HP:0002359
- **Defeitos da cadeia respiratória mitocondrial** — HPO: HP:0200125
- **Dificuldade para ficar em pé** — HPO: HP:0003698
- **Atrofia da fibra muscular** — HPO: HP:0100295
- **Metabolismo anormal de glicoesfingolipídios** — HPO: HP:0004343
- **Hiperesplenismo** — HPO: HP:0001971
- **Nível elevado de colina cerebral por EMR** — HPO: HP:0012706
- **Clônus do tornozelo** — HPO: HP:0011448
- _...e mais 328 sintomas. Ver https://raras.org/doenca/demencia-relacionada-com-lipidose-cerebral._

## Genes associados (15)

- **GRN** — Progranulin [Disease-causing germline mutation(s) in]
  - Função: Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807
- **ATP13A2** — Polyamine-transporting ATPase 13A2 [Candidate gene tested 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
- **HEXA** — Beta-hexosaminidase subunit alpha [Disease-causing germline mutation(s) in]
  - Função: Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from cert
- **CLN6** — Ceroid-lipofuscinosis neuronal protein 6 [Disease-causing germline mutation(s) in]
- **GBA1** — Lysosomal acid glucosylceramidase [Disease-causing germline mutation(s) in]
  - Função: Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-
- **SCARB2** — Lysosome membrane protein 2 [Candidate gene tested in]
  - Função: Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting (Microbial infection) Acts as a receptor for enterovirus 71
- **GALC** — Galactocerebrosidase [Candidate gene tested in]
  - Função: Hydrolyzes the galactose ester bonds of glycolipids such as galactosylceramide and galactosylsphingosine (PubMed:8281145, PubMed:8399327). Enzyme with very low activity responsible for the lysosomal c
- **CLN8** — Protein CLN8 [Disease-causing germline mutation(s) in]
  - Função: Could play a role in cell proliferation during neuronal differentiation and in protection against cell death
- **DNAJC5** — DnaJ homolog subfamily C member 5 [Disease-causing germline mutation(s) in]
  - Função: Acts as a general chaperone in regulated exocytosis (By similarity). Acts as a co-chaperone for the SNARE protein SNAP-25 (By similarity). Involved in the calcium-mediated control of a late stage of e
- **TPP1** — Tripeptidyl-peptidase 1 [Disease-causing germline mutation(s) in]
  - Função: Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:11054422, PubMed:19038966, PubMed:19038967). May act as a non-specific lysosomal peptidase which generates tripeptides from the
- **CYP27A1** — Sterol 26-hydroxylase, mitochondrial [Disease-causing germline mutation(s) in]
  - Função: Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol
- **CTSF** — Cathepsin F [Disease-causing germline mutation(s) in]
  - Função: Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis
- **CTSD** — Cathepsin D [Disease-causing germline mutation(s) in]
  - Função: Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pa
- **HEXB** — Beta-hexosaminidase subunit beta [Disease-causing germline mutation(s) in]
  - Função: Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from cert
- **CLN3** — Battenin [Disease-causing germline mutation(s) in]
  - Função: Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as reg

## Medicamentos em desenvolvimento (6)

- CHENODIOL — Fase Phase 4 (Bile acid receptor FXR agonist)
- MIGLUSTAT — Fase Phase 3 (Ceramide glucosyltransferase inhibitor)
- VENGLUSTAT — Fase Phase 3 (Ceramide glucosyltransferase inhibitor)
- TRENONACOG ALFA — Fase Phase 2 (Coagulation factor IX exogenous protein)
- MYCOPHENOLATE MOFETIL — Fase Phase 2 (Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor)
- LOVASTATIN — Fase Phase 2 (HMG-CoA reductase inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0020143

## Ensaios clínicos ativos (5)

- **NCT05473637** [RECRUITING]: Taiwan Associated Genetic and Nongenetic Small Vessel Disease — https://clinicaltrials.gov/study/NCT05473637
- **NCT02699190** [COMPLETED]: LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies — https://clinicaltrials.gov/study/NCT02699190
- **NCT03047369** [RECRUITING]: The Myelin Disorders Biorepository Project — https://clinicaltrials.gov/study/NCT03047369
- **NCT01793168** [RECRUITING]: Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford — https://clinicaltrials.gov/study/NCT01793168
- **NCT06539169** [RECRUITING]: FLOWER: Following Longitudinal Outcomes With Epidemiology for Rare Diseases — https://clinicaltrials.gov/study/NCT06539169

## Doenças relacionadas (por similaridade fenotípica)

- [Gangliosidose GM2](https://raras.org/doenca/gangliosidose-gm2) — ORPHA:309152 — 145 sintomas em comum
- [Lipofuscinose ceroide neuronal](https://raras.org/doenca/lipofuscinose-ceroide-neuronal) — ORPHA:216 — 128 sintomas em comum
- [doença da síntese de ácidos biliares](https://raras.org/doenca/doenca-da-sintese-de-acidos-biliares) — ORPHA:79168 — 114 sintomas em comum
- [Xantomatose cerebrotendinosa](https://raras.org/doenca/xantomatose-cerebrotendinosa) — ORPHA:909 — 113 sintomas em comum
- [Epilepsia, mioclonia progressiva](https://raras.org/doenca/epilepsia-mioclonia-progressiva) — ORPHA:98261 — 95 sintomas em comum
- [Doença Sandhoff](https://raras.org/doenca/doenca-sandhoff) — ORPHA:796 — 90 sintomas em comum
- [Doença de Krabbe](https://raras.org/doenca/doenca-de-krabbe) — ORPHA:487 — 87 sintomas em comum
- [Ataxia espástica](https://raras.org/doenca/ataxia-espastica) — ORPHA:316226 — 82 sintomas em comum
- [Doença Tay-Sachs](https://raras.org/doenca/doenca-tay-sachs) — ORPHA:845 — 78 sintomas em comum
- [Necrose avascular](https://raras.org/doenca/necrose-avascular) — ORPHA:399164 — 72 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.

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**Citação sugerida**: Raras.org — Demência relacionada com lipidose cerebral. Disponível em: https://raras.org/doenca/demencia-relacionada-com-lipidose-cerebral
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