# Amaurose congênita de Leber

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

## Identificadores

- **ORPHA**: 65 — https://www.orpha.net/en/disease/detail/65
- **CID-10**: H35.5
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A Amaurose Congênita de Leber (ACL) é uma doença da retina (a parte do olho que capta a luz) que causa cegueira. Ela é diagnosticada quando as respostas a exames que medem a atividade elétrica da retina (como o eletroretinograma de Ganzfeld, ou ERG) estão muito abaixo do normal ou são praticamente inexistentes. A condição está associada a uma perda visual grave que surge já no primeiro ano de vida da criança.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive

## Sinais e sintomas (93 fenótipos HPO)

- **Atenuação dos vasos sanguíneos da retina** — HPO: HP:0007843
- **Hipoplasia do vermis cerebelar** — HPO: HP:0001320
- **Eletrorretinograma indetectável adaptado à luz e ao escuro** — HPO: HP:0007688
- **Distrofia de cones/cones e bastonetes** — HPO: HP:0000548
- **Atrofia coriocapilar** — HPO: HP:0030491
- **Hipertreoninemia** — HPO: HP:0003354
- **Reflexo foveal opaco** — HPO: HP:0034362
- **Visão ultrabaixa com projeção de movimento retida** — HPO: HP:0032284
- **Hemeralopia** — HPO: HP:0012047
- **Atrofia peripapilar** — HPO: HP:0500087
- **Perseguição suave prejudicada** — HPO: HP:0007772
- **Perda visual** — HPO: HP:0000572
- **Distrofia de cones e bastonetes** — HPO: HP:0000510
- **Palidez** — HPO: HP:0000980
- **Quedas** — HPO: HP:0002527
- **Distrofia retiniana** — HPO: HP:0000556
- **Hiposmia** — HPO: HP:0004409
- **Pigmentação numular do fundo de olho** — HPO: HP:0030505
- **Olho profundamente inserido** — HPO: HP:0000490
- **Defeito do campo visual** — HPO: HP:0001123
- **Atraso de crescimento** — HPO: HP:0001510
- **Hipertreoninúria** — HPO: HP:0003296
- **Deficiência auditiva neurossensorial** — HPO: HP:0000407
- **Atrofia do fundo de olho** — HPO: HP:0001099
- **Amplitude diminuída do eletrorretinograma adaptado ao claro e ao escuro** — HPO: HP:0000654
- **Deficiência visual** — HPO: HP:0000505
- **Hepatomegalia** — HPO: HP:0002240
- **Miopia** — HPO: HP:0000545
- **Degeneração retiniana** — HPO: HP:0000546
- **Nistagmo pendular** — HPO: HP:0012043
- **Adelgaçamento retiniano** — HPO: HP:0030329
- **Maculopatia em olho de boi** — HPO: HP:0011504
- **Acuidade visual moderadamente reduzida** — HPO: HP:0030515
- **Hialose asteroide** — HPO: HP:0030672
- **Morfologia anormal do humor vítreo** — HPO: HP:0004327
- **Constrição arteriolar retiniana** — HPO: HP:0008043
- **Atrofia retiniana periférica** — HPO: HP:0200070
- **Ausência de reflexo foveal** — HPO: HP:0030825
- **Hipermetropia alta** — HPO: HP:0008499
- **Estrabismo** — HPO: HP:0000486
- _...e mais 53 sintomas. Ver https://raras.org/doenca/amaurose-congenita-de-leber._

## Genes associados (22)

- **RDH12** — Retinol dehydrogenase 12 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Retinoids dehydrogenase/reductase with a clear preference for NADP. Displays high activity towards 9-cis, 11-cis and all-trans-retinal. Shows very weak activity towards 13-cis-retinol (PubMed:12226107
- **AIPL1** — Aryl-hydrocarbon-interacting protein-like 1 [Disease-causing germline mutation(s) in]
  - Função: May be important in protein trafficking and/or protein folding and stabilization
- **SPATA7** — Spermatogenesis-associated protein 7 [Disease-causing germline mutation(s) in]
  - Função: Involved in the maintenance of both rod and cone photoreceptor cells (By similarity). It is required for recruitment and proper localization of RPGRIP1 to the photoreceptor connecting cilium (CC), as
- **KCNJ13** — Inward rectifier potassium channel 13 [Disease-causing germline mutation(s) in]
  - Função: Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration o
- **CEP290** — Centrosomal protein of 290 kDa [Disease-causing germline mutation(s) in]
  - Função: Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559). May play a role in early ciliogenesi
- **CRX** — Cone-rod homeobox protein [Disease-causing germline mutation(s) in]
  - Função: Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with ot
- **PCYT1A** — Choline-phosphate cytidylyltransferase A [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis
- **LRAT** — Lecithin retinol acyltransferase [Disease-causing germline mutation(s) in]
  - Função: Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters (PubMed:9920938). Retinyl esters are storage forms of vitamin A (Probabl
- **GUCY2D** — Retinal guanylyl cyclase 1 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Catalyzes the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors. Plays an essential role in phototransduction, by mediating cGMP replenishment (PubMed:15123990, PubMed:21928830, PubMe
- **IQCB1** — IQ calmodulin-binding motif-containing protein 1 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Involved in ciliogenesis. The function in an early step in cilia formation depends on its association with CEP290/NPHP6 (PubMed:21565611, PubMed:23446637). Involved in regulation of the BBSome complex
- **CRB1** — Protein crumbs homolog 1 [Disease-causing germline mutation(s) in]
  - Função: Plays a role in photoreceptor morphogenesis in the retina (By similarity). May maintain cell polarization and adhesion (By similarity)
- **TUBB4B** — Tubulin beta-4B chain [Disease-causing germline mutation(s) in]
  - Função: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the additio
- **IMPDH1** — Inosine-5'-monophosphate dehydrogenase 1 [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays
- **RPGRIP1** — X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: May function as scaffolding protein. Required for normal location of RPGR at the connecting cilium of photoreceptor cells. Required for normal disk morphogenesis and disk organization in the outer seg
- **USP45** — Ubiquitin carboxyl-terminal hydrolase 45 [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the deubiquitination of SPDL1 (PubMed:30258100). Plays a role in the repair of UV-induced DNA damage via deubiquitination of ERCC1, promoting its recruitment to DNA damage sites (PubMed:2553

## Medicamentos em desenvolvimento (4)

- VORETIGENE NEPARVOVEC — Fase Phase 4 (Retinoid isomerohydrolase exogenous gene)
- PREDNISOLONE — Fase Phase 1 (Glucocorticoid receptor agonist)
- PREDNISONE — Fase Phase 1 (Glucocorticoid receptor agonist)
- SEPOFARSEN — Fase Phase 1 (CEP290 mRNA positive modulator)
- Fonte: https://platform.opentargets.org/disease/MONDO_0018998

## Ensaios clínicos ativos (14)

- **NCT06891443** [RECRUITING]: Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION) — https://clinicaltrials.gov/study/NCT06891443
- **NCT01793168** [RECRUITING]: Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford — https://clinicaltrials.gov/study/NCT01793168
- **NCT02435940** [RECRUITING]: Inherited Retinal Degenerative Disease Registry — https://clinicaltrials.gov/study/NCT02435940
- **NCT05906953** [RECRUITING]: Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR) — https://clinicaltrials.gov/study/NCT05906953
- **NCT03655223** [ENROLLING_BY_INVITATION]: Early Check: Expanded Screening in Newborns — https://clinicaltrials.gov/study/NCT03655223
- **NCT05203939** [ACTIVE_NOT_RECRUITING]: Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis — https://clinicaltrials.gov/study/NCT05203939
- **NCT00481546** [ACTIVE_NOT_RECRUITING]: Phase I Trial of Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations — https://clinicaltrials.gov/study/NCT00481546
- **NCT01208389** [ACTIVE_NOT_RECRUITING]: Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2 — https://clinicaltrials.gov/study/NCT01208389
- **NCT00999609** [ACTIVE_NOT_RECRUITING]: Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis — https://clinicaltrials.gov/study/NCT00999609
- **NCT06088992** [ACTIVE_NOT_RECRUITING]: Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT) — https://clinicaltrials.gov/study/NCT06088992

## Centros de referência no Brasil (24)

- Hospital Universitário Prof. Edgard Santos (HUPES) (Salvador/BA)
- Hospital Infantil Albert Sabin (Fortaleza/CE)
- Hospital de Apoio de Brasília (HAB) (Brasília/DF)
- Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIABA) (Vila Velha/ES)
- Hospital das Clínicas da UFG (Goiânia/GO)
- Hospital Universitário da UFJF (Juiz de Fora/MG)
- Hospital das Clínicas da UFMG (Belo Horizonte/MG)
- Hospital Universitário Julio Müller (HUJM) (Cuiabá/MT)
- Hospital Universitário João de Barros Barreto (Belém/PA)
- Hospital Universitário Lauro Wanderley (HULW) (João Pessoa/PB)
- Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) (Recife/PE)
- Hospital Pequeno Príncipe (Curitiba/PR)
- Hospital Universitário Regional de Maringá (HUM) (Maringá/PR)
- Hospital de Clínicas da UFPR (Curitiba/PR)
- Hospital Universitário Pedro Ernesto (HUPE-UERJ) (Rio de Janeiro/RJ)
- Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz) (Rio de Janeiro/RJ)
- Hospital São Lucas da PUCRS (Porto Alegre/RS)
- Hospital de Clínicas de Porto Alegre (HCPA) (Porto Alegre/RS)
- Hospital Universitário da UFSC (HU-UFSC) (Florianópolis/SC)
- Hospital das Clínicas da FMUSP (São Paulo/SP)

## Doenças relacionadas (por similaridade fenotípica)

- [Retinite pigmentosa](https://raras.org/doenca/retinite-pigmentosa) — ORPHA:791 — 55 sintomas em comum
- [Distrofia dos cones e bastonetes](https://raras.org/doenca/distrofia-dos-cones-e-bastonetes) — ORPHA:1872 — 42 sintomas em comum
- [Ciliopatia retiniana](https://raras.org/doenca/ciliopatia-retiniana) — ORPHA:156165 — 29 sintomas em comum
- [Síndrome Usher](https://raras.org/doenca/sindrome-usher) — ORPHA:886 — 26 sintomas em comum
- [Síndrome Walker-Warburg](https://raras.org/doenca/899) — ORPHA:899 — 25 sintomas em comum
- [Uveíte](https://raras.org/doenca/uveite) — ORPHA:98715 — 25 sintomas em comum
- [Doença de Stargardt](https://raras.org/doenca/doenca-de-stargardt) — ORPHA:827 — 24 sintomas em comum
- [Cegueira noturna estacionária congênita](https://raras.org/doenca/cegueira-noturna-estacionaria-congenita) — ORPHA:215 — 24 sintomas em comum
- [Síndrome Joubert com defeito oculorrenal](https://raras.org/doenca/sindrome-joubert-com-defeito-oculorrenal) — ORPHA:2318 — 24 sintomas em comum
- [Doença da visão cromática](https://raras.org/doenca/doenca-da-visao-cromatica) — ORPHA:98658 — 23 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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