# Neuropatia motora distal hereditária

> Página oficial: https://raras.org/doenca/neuropatia-motora-distal-hereditaria
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 53739 — https://www.orpha.net/en/disease/detail/53739
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Doença rara que causa fraqueza e atrofia muscular progressiva, principalmente nos membros distais. Pode apresentar rigidez articular, ataxia, anartria e, em alguns casos, encefalopatia.

## Epidemiologia e herança


## Sinais e sintomas (228 fenótipos HPO)

- **Atrofia muscular espinhal** — HPO: HP:0007269
- **Caquexia** — HPO: HP:0004326
- **Rigidez articular** — HPO: HP:0001387
- **Fraqueza muscular de membro** — HPO: HP:0003690
- **Hipoplasia do corpo caloso** — HPO: HP:0002079
- **Ataxia espástica** — HPO: HP:0002497
- **Encefalopatia progressiva** — HPO: HP:0002448
- **Anartria** — HPO: HP:0002425
- **Tetraparesia espástica** — HPO: HP:0001285
- **Atrofia óptica** — HPO: HP:0000648
- **Dificuldade para ficar em pé** — HPO: HP:0003698
- **Atrofia cerebelar** — HPO: HP:0001272
- **Disartria** — HPO: HP:0001260
- **Paraparesia espástica progressiva** — HPO: HP:0007199
- **Hipotonia generalizada** — HPO: HP:0001290
- **Déficit de crescimento** — HPO: HP:0001508
- **Incontinência urinária** — HPO: HP:0000020
- **Camptodactilia do dedo** — HPO: HP:0100490
- **Constipação** — HPO: HP:0002019
- **Dependência de ventilador com incapacidade de desmame** — HPO: HP:0005946
- **Anormalidade da musculatura do pé** — HPO: HP:0001436
- **Polineuropatia motora** — HPO: HP:0007178
- **Pé valgo** — HPO: HP:0008081
- **Atraso de crescimento** — HPO: HP:0001510
- **Hipoparatireoidismo** — HPO: HP:0000829
- **Convulsão** — HPO: HP:0001250
- **Acúmulo de ferro na substância negra** — HPO: HP:0012678
- **Hipotonia neonatal** — HPO: HP:0001319
- **Hiperidrose** — HPO: HP:0000975
- **Degeneração das células do corno anterior** — HPO: HP:0002398
- **Velocidade de condução nervosa diminuída** — HPO: HP:0000762
- **Retardo do crescimento intrauterino** — HPO: HP:0001511
- **Pequeno para a idade gestacional** — HPO: HP:0001518
- **Denervação do diafragma** — HPO: HP:0009109
- **Insuficiência respiratória** — HPO: HP:0002878
- **Dissecção da aorta ascendente** — HPO: HP:0004933
- **Fraqueza do tornozelo** — HPO: HP:0031374
- **Suscetibilidade a hematomas** — HPO: HP:0000978
- **Neuropatia sensorimotora** — HPO: HP:0007141
- **Choro fraco** — HPO: HP:0001612
- _...e mais 188 sintomas. Ver https://raras.org/doenca/neuropatia-motora-distal-hereditaria._

## Genes associados (25)

- **GARS1** — Glycine--tRNA ligase [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:24898252, PubMed:28675565
- **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
- **COQ7** — NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the hydroxylation of the 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone at the C6 position and participates in the biosynthesis of ubiquinone (Probable). Catalyzes the reaction thro
- **DNAJB2** — DnaJ homolog subfamily B member 2 [Disease-causing germline mutation(s) in]
  - Função: Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:22219199, PubMed:7957263). In parallel,
- **PLEKHG5** — Pleckstrin homology domain-containing family G member 5 [Disease-causing germline mutation(s) in]
  - Função: Functions as a guanine exchange factor (GEF) for RAB26 and thus regulates autophagy of synaptic vesicles in axon terminal of motoneurons (By similarity). Involved in the control of neuronal cell diffe
- **BAG3** — BAG family molecular chaperone regulator 3 [Disease-causing germline mutation(s) in]
  - Função: Co-chaperone and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g. HSPA1A/HSP70 or HSPA8/HSC70, and small heat shock proteins (sHS
- **SIGMAR1** — Sigma non-opioid intracellular receptor 1 [Disease-causing germline mutation(s) in]
  - Função: Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma memb
- **HSPB3** — Heat shock protein beta-3 [Disease-causing germline mutation(s) in]
  - Função: Inhibitor of actin polymerization
- **HSPB8** — Heat shock protein beta-8 [Disease-causing germline mutation(s) in]
  - Função: Involved in the chaperone-assisted selective autophagy (CASA), a crucial process for protein quality control, particularly in mechanical strained cells and tissues such as muscle. Displays temperature
- **VRK1** — Serine/threonine-protein kinase VRK1 [Disease-causing germline mutation(s) in]
  - Função: Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response (PubMed:14645249, PubMed:
- **FBXO38** — F-box only protein 38 [Disease-causing germline mutation(s) in]
  - Função: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of PDCD1/PD-1, thereby r
- **ATP7A** — Copper-transporting ATPase 1 [Disease-causing germline mutation(s) in]
  - Função: ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:10419525, PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires Cu(+) io
- **HSPB1** — Heat shock protein beta-1 [Disease-causing germline mutation(s) in]
  - Função: Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state (PubMed:10383393, PubMed:20178975). Plays a role in stress resist
- **SORD** — Sorbitol dehydrogenase [Disease-causing germline mutation(s) in]
  - Função: Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols. Is mostly active with D-sorbitol (D-glucitol), L-threitol, xylitol and ribitol as substrates, l
- **SPTAN1** — Spectrin alpha chain, non-erythrocytic 1 [Disease-causing germline mutation(s) in]
  - Função: Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane

## Medicamentos em desenvolvimento (1)

- ONASEMNOGENE ABEPARVOVEC — Fase Phase 3 (Survival motor neuron protein exogenous gene)
- Fonte: https://platform.opentargets.org/disease/MONDO_0018894

## Ensaios clínicos ativos (1)

- **NCT04193228** [COMPLETED]: Muscle Structure, Function and Gait in dHMN — https://clinicaltrials.gov/study/NCT04193228

## Doenças relacionadas (por similaridade fenotípica)

- [Neuropatia motora hereditária distal autossômica dominante](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-dominante) — ORPHA:140465 — 140 sintomas em comum
- [Neuropatia motora hereditária distal autossômica recessiva](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-recessiva) — ORPHA:140468 — 136 sintomas em comum
- [Doença de Charcot-Marie-Tooth tipo 4](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4) — ORPHA:64749 — 84 sintomas em comum
- [Atrofia muscular espinhal proximal](https://raras.org/doenca/atrofia-muscular-espinhal-proximal) — ORPHA:70 — 80 sintomas em comum
- [Miopatia distal autossômica dominante](https://raras.org/doenca/miopatia-distal-autossomica-dominante) — ORPHA:206650 — 71 sintomas em comum
- [Doença de Charcot-Marie-Tooth intermediária](https://raras.org/doenca/doenca-de-charcot-marie-tooth-intermediaria) — ORPHA:476123 — 66 sintomas em comum
- [Miopatia nemalínica](https://raras.org/doenca/miopatia-nemalinica) — ORPHA:607 — 63 sintomas em comum
- [Deficiência qualitativa ou quantitativa da tropomiosina](https://raras.org/doenca/deficiencia-qualitativa-ou-quantitativa-da-tropomiosina) — ORPHA:284790 — 62 sintomas em comum
- [Deficiências qualitativas e quantitativas de nebulina](https://raras.org/doenca/deficiencias-qualitativas-e-quantitativas-de-nebulina) — ORPHA:209182 — 60 sintomas em comum
- [Deficiências qualitativas e quantitativas da alfa-actina](https://raras.org/doenca/deficiencias-qualitativas-e-quantitativas-da-alfa-actina) — ORPHA:209059 — 60 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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