# Leucodistrofia

> Página oficial: https://raras.org/doenca/leucodistrofia
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-13

## Identificadores

- **ORPHA**: 68356 — https://www.orpha.net/en/disease/detail/68356
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Leucodistrofias são um grupo de doenças genéticas raras, progressivas e metabólicas que afetam o cérebro, a medula espinhal e, muitas vezes, os nervos periféricos. Cada tipo de leucodistrofia é causado por uma alteração genética específica que leva ao desenvolvimento anormal ou à destruição da substância branca (a bainha de mielina) do cérebro. A bainha de mielina é o revestimento protetor dos nervos e, sem ela, os nervos não conseguem funcionar normalmente. Cada tipo de leucodistrofia afeta uma parte diferente da bainha de mielina, o que leva a uma variedade de problemas neurológicos.

## Epidemiologia e herança


## Sinais e sintomas (1152 fenótipos HPO)

- **Estrabismo** — HPO: HP:0000486
- **Anormalidade inflamatória do olho** — HPO: HP:0100533
- **Hiperpigmentação generalizada** — HPO: HP:0007440
- **Anormalidade do esmalte dentário** — HPO: HP:0000682
- **Arritmia** — HPO: HP:0011675
- **Anormalidade da língua** — HPO: HP:0000157
- **Cristas supraorbitais subdesenvolvidas** — HPO: HP:0009891
- **Agitação** — HPO: HP:0000713
- **Proptose** — HPO: HP:0000520
- **Morfologia anormal da pálpebra** — HPO: HP:0000492
- **Morfologia vascular retiniana anormal** — HPO: HP:0008046
- **Anormalidade do tendão de Aquiles** — HPO: HP:0005109
- **Transtorno de personalidade** — HPO: HP:0012075
- **Morfologia anormal do septo atrial** — HPO: HP:0011994
- **Anormalidade dos processos espinhosos vertebrais** — HPO: HP:0008516
- **Fibras nervosas retinianas hipermielinizadas** — HPO: HP:0007922
- **Perda prematura de dentes** — HPO: HP:0006480
- **Aterosclerose prematura da artéria coronária** — HPO: HP:0005181
- **Aterosclerose precoce** — HPO: HP:0004416
- **Morfologia anormal do globo pálido** — HPO: HP:0002453
- **Anormalidade do dedo** — HPO: HP:0001167
- **Morfologia anormal da orelha externa** — HPO: HP:0000377
- **Morfologia pulmonar anormal** — HPO: HP:0002088
- **Defeitos da cadeia respiratória mitocondrial** — HPO: HP:0200125
- **Ideação suicida** — HPO: HP:0031589
- **Catarata juvenil** — HPO: HP:0001118
- **Estenose pilórica** — HPO: HP:0002021
- **Anormalidade da coagulação** — HPO: HP:0001928
- **Prega cutânea nucal espessada** — HPO: HP:0000474
- **Má absorção** — HPO: HP:0002024
- **Anormalidade corioretiniana** — HPO: HP:0000532
- **Displasia renal multicística** — HPO: HP:0000003
- **Opacidade corneana** — HPO: HP:0007957
- **Nível elevado de lactato cerebral por EMR** — HPO: HP:0012707
- **Anormalidade do cotovelo** — HPO: HP:0009811
- **Aparência de envelhecimento prematuro** — HPO: HP:0007495
- **Aumento da suscetibilidade a fraturas** — HPO: HP:0002659
- **Sinais de trato longo** — HPO: HP:0002423
- **Potenciais evocados motores anormais** — HPO: HP:0012896
- **Anormalidade da morfologia da tíbia** — HPO: HP:0002992
- _...e mais 1112 sintomas. Ver https://raras.org/doenca/leucodistrofia._

## Genes associados (62)

- **DARS1** — Aspartate--tRNA ligase, cytoplasmic [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of th
- **NDUFA2** — NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 [Candidate gene tested in]
  - Função: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons fro
- **NKX6-2** — Homeobox protein Nkx-6.2 [Candidate gene tested in]
  - 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 o
- **SCP2** — Synaptonemal complex protein 2 [Candidate gene tested in]
  - Função: Major component of the axial/lateral elements of synaptonemal complexes (SCS) during meiotic prophase. Plays a role in the assembly of synaptonemal complexes. Required for normal meiotic chromosome sy
- **ALDH3A2** — Aldehyde dehydrogenase family 3 member A2 [Candidate gene tested in]
  - Função: Catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length (PubMed:180
- **NADK2** — NAD kinase 2, mitochondrial [Candidate gene tested in]
  - Função: Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH
- **EIF2B4** — Translation initiation factor eIF2B subunit delta [Candidate gene tested in]
  - Função: Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, PubMed
- **MLC1** — Membrane protein MLC1 [Candidate gene tested in]
  - Função: Transmembrane protein mainly expressed in brain astrocytes that may play a role in transport across the blood-brain and brain-cerebrospinal fluid barriers (PubMed:22328087). Regulates the response of
- **PEX11B** — Peroxisomal membrane protein 11B [Candidate gene tested in]
  - Função: Involved in peroxisomal proliferation (PubMed:9792670). May regulate peroxisome division by recruiting the dynamin-related GTPase DNM1L to the peroxisomal membrane (PubMed:12618434). Promotes membrane
- **PEX19** — Peroxisomal biogenesis factor 19 [Candidate gene tested in]
  - Função: Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cy
- **ASPA** — Aspartoacylase [Candidate gene tested in]
  - Função: Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintena
- **MAL** — Myelin and lymphocyte protein [Candidate gene tested in]
  - Função: May be involved in vesicular trafficking from the Golgi apparatus to the cell membrane. Plays a role in the maintenance of the myelin sheath, and in axon-glia and glia-glia interactions
- **LSM11** — U7 snRNA-associated Sm-like protein LSm11 [Candidate gene tested in]
  - Função: Component of the U7 snRNP complex that is involved in the histone 3'-end pre-mRNA processing (PubMed:11574479, PubMed:16914750, PubMed:33230297). Increases U7 snRNA levels but not histone 3'-end pre-m
- **TREX1** — Three-prime repair exonuclease 1 [Candidate gene tested in]
  - Função: Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:10393201, PubMed:17293595). Preven
- **RNASEH2C** — Ribonuclease H2 subunit C [Candidate gene tested in]
  - Função: Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki f

## Medicamentos em desenvolvimento (9)

- CHENODIOL — Fase Phase 4 (Bile acid receptor FXR agonist)
- ATIDARSAGENE AUTOTEMCEL — Fase Phase 4 (ARSA exogenous gene)
- LERIGLITAZONE — Fase Phase 3 (Peroxisome proliferator-activated receptor gamma agonist)
- ELIVALDOGENE AUTOTEMCEL — Fase Phase 3 (ABCD1 exogenous gene)
- PIOGLITAZONE — Fase Phase 2 (Peroxisome proliferator-activated receptor gamma agonist)
- BARICITINIB — Fase Phase 2 (Tyrosine-protein kinase JAK2 inhibitor)
- LOVASTATIN — Fase Phase 2 (HMG-CoA reductase inhibitor)
- LEVETIRACETAM — Fase Phase 1 (Voltage-gated N-type calcium channel alpha-1B subunit blocker)
- PREDNISONE — Fase Phase 1 (Glucocorticoid receptor agonist)
- Fonte: https://platform.opentargets.org/disease/MONDO_0019046

## Ensaios clínicos ativos (16)

- **NCT03333200** [RECRUITING]: Longitudinal Study of Neurodegenerative Disorders — https://clinicaltrials.gov/study/NCT03333200
- **NCT03639285** [RECRUITING]: Natural History, Diagnosis, and Outcomes for Leukodystrophies — https://clinicaltrials.gov/study/NCT03639285
- **NCT03047369** [RECRUITING]: The Myelin Disorders Biorepository Project — https://clinicaltrials.gov/study/NCT03047369
- **NCT04925349** [RECRUITING]: Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia — https://clinicaltrials.gov/study/NCT04925349
- **NCT02254863** [RECRUITING]: UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells — https://clinicaltrials.gov/study/NCT02254863
- **NCT07046338** [RECRUITING]: Lentiviral Hematopoietic Stem Cell Gene Therapy for MLD — https://clinicaltrials.gov/study/NCT07046338
- **NCT03725670** [RECRUITING]: Direct Lentiviral Injection Gene Therapy for MLD — https://clinicaltrials.gov/study/NCT03725670
- **NCT01793168** [RECRUITING]: Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford — https://clinicaltrials.gov/study/NCT01793168
- **NCT05443906** [RECRUITING]: Home Exercise for Individuals with Neurodegenerative Disease — https://clinicaltrials.gov/study/NCT05443906
- **NCT05368038** [ENROLLING_BY_INVITATION]: ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program — https://clinicaltrials.gov/study/NCT05368038

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- [Duplicação/triplicação parcial do cromossomo 5](https://raras.org/doenca/duplicacaotriplicacao-parcial-do-cromossomo-5) — ORPHA:262211 — 151 sintomas em comum
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- [Doença de Krabbe](https://raras.org/doenca/doenca-de-krabbe) — ORPHA:487 — 143 sintomas em comum
- [Deficiência de complexo III isolada](https://raras.org/doenca/deficiencia-de-complexo-iii-isolada) — ORPHA:1460 — 131 sintomas em comum
- [Adrenoleucodistrofia ligada ao X](https://raras.org/doenca/adrenoleucodistrofia-ligada-ao-x) — ORPHA:43 — 131 sintomas em comum
- [Encefalopatia epiléptica de início precoce inespecífica](https://raras.org/doenca/encefalopatia-epileptica-de-inicio-precoce-inespecifica) — ORPHA:442835 — 127 sintomas em comum
- [Síndrome epiléptico de início neonatal-infantil](https://raras.org/doenca/sindrome-epileptico-de-inicio-neonatal-infantil) — ORPHA:693802 — 126 sintomas em comum
- [Disease Pelizaeus-Merzbacher](https://raras.org/doenca/disease-pelizaeus-merzbacher) — ORPHA:702 — 124 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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