# Linfohistiocitose hemofagocítica familiar

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

## Identificadores

- **ORPHA**: 540 — https://www.orpha.net/en/disease/detail/540
- **CID-10**: D76.1
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

É um caso de linfo-histiocitose hemofagocítica (LHH) causado por uma alteração genética que a pessoa herdou.

## Epidemiologia e herança

- **Prevalência**: Unknown
- **Padrão de herança**: Autosomal recessive

## Sinais e sintomas (204 fenótipos HPO)

- **Hipersensibilidade tardia reduzida** — HPO: HP:0002972
- **Febre periódica** — HPO: HP:0032323
- **Linfopenia** — HPO: HP:0001888
- **Pescoço alado** — HPO: HP:0000465
- **Concentração elevada de fator de necrose tumoral alfa circulante** — HPO: HP:6000239
- **Atraso no desenvolvimento da habilidade de ficar em pé** — HPO: HP:0030371
- **Concentração elevada de CD25 solúvel circulante** — HPO: HP:0033833
- **Concentração elevada de alanina aminotransferase circulante** — HPO: HP:0031964
- **Atraso no desenvolvimento da marcha** — HPO: HP:0025808
- **Aumento da concentração circulante de interleucina 18** — HPO: HP:0034447
- **Concentração elevada de aspartato aminotransferase circulante** — HPO: HP:0031956
- **Nível elevado de gama-glutamiltransferase** — HPO: HP:0030948
- **Baixa estatura** — HPO: HP:0004322
- **Monocitopenia** — HPO: HP:0012312
- **Hepatite** — HPO: HP:0012115
- **Aumento da concentração circulante de interleucina 1 beta** — HPO: HP:6000374
- **Anormalidade da fisiologia do neutrófilo** — HPO: HP:0011990
- **Albinismo parcial** — HPO: HP:0007443
- **Náusea e vômito** — HPO: HP:0002017
- **Infecções respiratórias recorrentes** — HPO: HP:0002205
- **Aumento da proporção de mastócitos CD25+** — HPO: HP:0031408
- **Atrofia das cristas alveolares** — HPO: HP:0006308
- **Disfunção somatossensorial** — HPO: HP:0003474
- **Incapacidade de andar** — HPO: HP:0002540
- **Morfologia anormal de células natural killer** — HPO: HP:0012176
- **Função plaquetária anormal** — HPO: HP:0011869
- **Infecções estafilocócicas recorrentes** — HPO: HP:0007499
- **Sangramento anormal** — HPO: HP:0001892
- **Hiperpigmentação salpicada** — HPO: HP:0005585
- **Derrame pleural** — HPO: HP:0002202
- **Neuropatia sensorial** — HPO: HP:0000763
- **Anormalidade da pigmentação retiniana** — HPO: HP:0007703
- **Nistagmo rotatório** — HPO: HP:0001583
- **Linfócitos vacuolizados** — HPO: HP:0001922
- **Morfologia anormal de leucócitos** — HPO: HP:0001881
- **Parkinsonismo** — HPO: HP:0001300
- **Atrofia cerebelar** — HPO: HP:0001272
- **Paraplegia espástica** — HPO: HP:0001258
- **Demência** — HPO: HP:0000726
- **Grandes aglomerados de pigmento irregularmente distribuídos ao longo da haste capilar** — HPO: HP:0004527
- _...e mais 164 sintomas. Ver https://raras.org/doenca/linfohistiocitose-hemofagocitica-familiar._

## Genes associados (9)

- **UNC13D** — Protein unc-13 homolog D [Disease-causing germline mutation(s) in]
  - Função: Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late e
- **AP3B1** — AP-3 complex subunit beta-1 [Disease-causing germline mutation(s) in]
  - Função: Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes me
- **RC3H1** — Roquin-1 [Disease-causing germline mutation(s) in]
  - Função: Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ,
- **RAB27A** — Ras-related protein Rab-27A [Disease-causing germline mutation(s) in]
  - Função: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form a
- **LYST** — Lysosomal-trafficking regulator [Disease-causing germline mutation(s) in]
  - Função: Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes (PubMed:11984006, PubMed:25216107). Might regulate trafficking of effectors involved in exocytosis (PubMed:254
- **BLOC1S6** — Biogenesis of lysosome-related organelles complex 1 subunit 6 [Disease-causing germline mutation(s) in]
  - Função: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 comple
- **STX11** — Syntaxin-11 [Disease-causing germline mutation(s) in]
  - Função: SNARE that acts to regulate protein transport between late endosomes and the trans-Golgi network
- **PRF1** — Perforin-1 [Disease-causing germline mutation(s) in]
  - Função: Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:20889983, PubMed:21037563, PubMed:24558045, Pub
- **STXBP2** — Syntaxin-binding protein 2 [Disease-causing germline mutation(s) in]
  - Função: Involved in intracellular vesicle trafficking and vesicle fusion with membranes. Contributes to the granule exocytosis machinery through interaction with soluble N-ethylmaleimide-sensitive factor atta

## Ensaios clínicos ativos (5)

- **NCT03827343** [ACTIVE_NOT_RECRUITING]: Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer — https://clinicaltrials.gov/study/NCT03827343
- **NCT01966367** [ACTIVE_NOT_RECRUITING]: CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation — https://clinicaltrials.gov/study/NCT01966367
- **NCT01494103** [ACTIVE_NOT_RECRUITING]: Administration of Donor T Cells With the Caspase-9 Suicide Gene — https://clinicaltrials.gov/study/NCT01494103
- **NCT06587191** [ACTIVE_NOT_RECRUITING]: Emapalumab Efficacy in Children With Primary Hemophagocytic Lymphohistiocytosis — https://clinicaltrials.gov/study/NCT06587191
- **NCT06736080** [NOT_YET_RECRUITING]: Safety and Efficacy of Gene Therapy of FHL Type 3 Caused by Mutations in the Human UNC13D Gene by Transplantation of a Single Dose of Autologous CD34+ Cells Transduced Ex Vivo with the UNC13D LV Vector Expressing the UNC13D CDNA — https://clinicaltrials.gov/study/NCT06736080
- **NCT05744063** [COMPLETED]: A Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of pHLH in Treatment Experienced Chinese Patients — https://clinicaltrials.gov/study/NCT05744063
- **NCT05687474** [COMPLETED]: Baby Detect : Genomic Newborn Screening — https://clinicaltrials.gov/study/NCT05687474
- **NCT03312751** [COMPLETED]: Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis — https://clinicaltrials.gov/study/NCT03312751
- **NCT00368355** [COMPLETED]: T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts — https://clinicaltrials.gov/study/NCT00368355
- **NCT00006054** [TERMINATED]: Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies — https://clinicaltrials.gov/study/NCT00006054

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome Chediak-Higashi](https://raras.org/doenca/sindrome-chediak-higashi) — ORPHA:167 — 94 sintomas em comum
- [Síndrome de Hermansky-Pudlak](https://raras.org/doenca/sindrome-de-hermansky-pudlak) — ORPHA:79430 — 69 sintomas em comum
- [Doença do metabolismo do folato](https://raras.org/doenca/doenca-do-metabolismo-do-folato) — ORPHA:285657 — 46 sintomas em comum
- [Síndrome Hermansky-Pudlak devido a deficiência AP3B1](https://raras.org/doenca/sindrome-hermansky-pudlak-devido-a-deficiencia-ap3b1) — ORPHA:664500 — 46 sintomas em comum
- [Síndrome Hermansky-Pudlak por deficiência AP-3](https://raras.org/doenca/sindrome-hermansky-pudlak-por-deficiencia-ap-3) — ORPHA:183678 — 45 sintomas em comum
- [Síndrome Aicardi-Goutieres](https://raras.org/doenca/sindrome-aicardi-goutieres) — ORPHA:51 — 43 sintomas em comum
- [Síndrome Griscelli](https://raras.org/doenca/sindrome-griscelli) — ORPHA:381 — 42 sintomas em comum
- [Síndrome autoinflamatório associado aos proteassomas](https://raras.org/doenca/sindrome-autoinflamatorio-associado-aos-proteassomas) — ORPHA:324977 — 41 sintomas em comum
- [Síndrome JMP](https://raras.org/doenca/sindrome-jmp) — ORPHA:324999 — 41 sintomas em comum
- [Síndrome Nakajo-Nishimura](https://raras.org/doenca/sindrome-nakajo-nishimura) — ORPHA:2615 — 41 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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**Citação sugerida**: Raras.org — Linfohistiocitose hemofagocítica familiar. Disponível em: https://raras.org/doenca/linfohistiocitose-hemofagocitica-familiar
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