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Neuropatia óptica hereditária de Leber
ORPHA:104CID-10 · H47.2CID-11 · 8C73.YOMIM 535000DOENÇA RARA

A Neuropatia Óptica Hereditária de Leber (LHON) é uma doença que afeta os nervos e piora com o tempo (neurodegenerativa), tendo origem nas mitocôndrias (as "usinas de energia" das nossas células). Ela atinge o nervo óptico (o "cabo" que leva a informação visual do olho para o cérebro) e, com frequência, provoca uma perda repentina da visão em jovens adultos que carregam essa condição.

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Introdução

O que você precisa saber de cara

📋

A Neuropatia Óptica Hereditária de Leber (LHON) é uma doença que afeta os nervos e piora com o tempo (neurodegenerativa), tendo origem nas mitocôndrias (as "usinas de energia" das nossas células). Ela atinge o nervo óptico (o "cabo" que leva a informação visual do olho para o cérebro) e, com frequência, provoca uma perda repentina da visão em jovens adultos que carregam essa condição.

Pesquisas ativas
9 ensaios
41 total registrados no ClinicalTrials.gov
Publicações científicas
890 artigos
Último publicado: 2026 Jan-Dec
Medicamentos
1 registrados
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Escala de raridade

CLASSIFICAÇÃO ORPHANET · BRASIL 2024
1-9 / 100 000
Ultra-rara
<1/50k
Muito rara
1/20k
Rara
1/10k
Pouco freq.
1/5k
Incomum
1/2k
Prevalência
2.6
Netherlands
Início
Adolescent
+ adult
🏥
SUS: Sem cobertura SUSScore: 0%
CID-10: H47.2
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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🧠
Neurológico
10 sintomas
👁️
Olhos
10 sintomas
❤️
Coração
4 sintomas
💪
Músculos
3 sintomas
🫁
Pulmão
1 sintomas
🫃
Digestivo
1 sintomas

+ 11 sintomas em outras categorias

Características mais comuns

90%prev.
Diminuição lenta da acuidade visual
Muito frequente (99-80%)
90%prev.
Defeitos da cadeia respiratória mitocondrial
Muito frequente (99-80%)
55%prev.
Perda visual progressiva
Frequente (79-30%)
55%prev.
Telangiectasia retiniana
Frequente (79-30%)
55%prev.
Tortuosidade vascular retiniana
Frequente (79-30%)
55%prev.
Atrofia óptica
Frequente (79-30%)
41sintomas
Muito frequente (2)
Frequente (8)
Ocasional (11)
Sem dados (20)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 41 características clínicas mais associadas, ordenadas por frequência.

Diminuição lenta da acuidade visualSlow decrease in visual acuity
Muito frequente (99-80%)90%
Defeitos da cadeia respiratória mitocondrialMitochondrial respiratory chain defects
Muito frequente (99-80%)90%
Perda visual progressivaProgressive visual loss
Frequente (79-30%)55%
Telangiectasia retinianaRetinal telangiectasia
Frequente (79-30%)55%
Tortuosidade vascular retinianaRetinal vascular tortuosity
Frequente (79-30%)55%

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2026
Total histórico890PubMed
Últimos 10 anos200publicações
Pico202585 papers
Linha do tempo
2026Hoje · 2026🧪 2005Primeiro ensaio clínico📈 2025Ano de pico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

12 genes identificados com associação a esta condição. Padrão de herança: Mitochondrial inheritance.

MT-CYBCytochrome bDisease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (3)
Respiratory electron transportComplex III assemblyMitochondrial translation termination
OUTRAS DOENÇAS (4)
mitochondrial diseaseLeber hereditary optic neuropathyhistiocytoid cardiomyopathymitochondrial complex III deficiency
HGNC:7427UniProt:P00156
MT-ATP6ATP synthase F(0) complex subunit aDisease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Subunit a, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (4)
Mitochondrial translation terminationFormation of ATP by chemiosmotic couplingCristae formationMitochondrial protein degradation
MECANISMO DE DOENÇA

Neuropathy, ataxia, and retinitis pigmentosa

A syndrome characterized by variable combination of developmental delay, psychomotor retardation, hearing loss, optic atrophy and retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy.

OUTRAS DOENÇAS (8)
mitochondrial diseasematernally-inherited Leigh syndromefamilial infantile bilateral striatal necrosismitochondrial proton-transporting ATP synthase complex deficiency
HGNC:7414UniProt:P00846
MT-CO3Cytochrome c oxidase subunit 3Disease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over t

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (5)
Cytoprotection by HMOX1Respiratory electron transportTP53 Regulates Metabolic GenesComplex IV assemblyMitochondrial translation termination
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (5)
mitochondrial diseasemitochondrial complex IV deficiency, nuclear-typeMELAS syndromehereditary recurrent myoglobinuria
HGNC:7422UniProt:P00414
DNAJC30DnaJ homolog subfamily C member 30, mitochondrialDisease-causing germline mutation(s) (loss of function) inTolerante
FUNÇÃO

Mitochondrial protein enriched in neurons that acts as a regulator of mitochondrial respiration (By similarity). Associates with the ATP synthase complex and facilitates ATP synthesis (By similarity). May be a chaperone protein involved in the turnover of the subunits of mitochondrial complex I N-module. It facilitates the degradation of N-module subunits damaged by oxidative stress, and contributes to complex I functional efficiency (PubMed:33465056)

LOCALIZAÇÃO

Mitochondrion inner membrane

EXPRESSÃO TECIDUAL(Ubíquo)
Testículo
27.4 TPM
Pituitária
18.9 TPM
Glândula adrenal
18.8 TPM
Tireoide
18.3 TPM
Brain Frontal Cortex BA9
15.8 TPM
INTERAÇÕES PROTEICAS (3)
OUTRAS DOENÇAS (3)
Leber-like hereditary optic neuropathy, autosomal recessive 1Williams syndromeLeber hereditary optic neuropathy
HGNC:16410UniProt:Q96LL9
MT-ND2NADH-ubiquinone oxidoreductase chain 2Disease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:16996290). Essential for the catalytic activity and assembly of complex I (PubMed:16996290)

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (4)
Respiratory electron transportComplex I biogenesisMitochondrial translation terminationMitochondrial protein degradation
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (4)
mitochondrial diseaseLeber hereditary optic neuropathymaternally-inherited Leigh syndromemitochondrial complex I deficiency
HGNC:7456UniProt:P03891
MT-ND6NADH-ubiquinone oxidoreductase chain 6Disease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:14595656, PubMed:8644732). Essential for the catalytic activity and assembly of complex I (PubMed:14595656, PubMed:8644732)

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (4)
Respiratory electron transportComplex I biogenesisMitochondrial translation terminationMitochondrial protein degradation
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (5)
mitochondrial diseaseLeber plus diseasematernally-inherited Leigh syndromeMELAS syndrome
HGNC:7462UniProt:P03923
MT-ND5NADH-ubiquinone oxidoreductase chain 5Disease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:15250827). Essential for the catalytic activity and assembly of complex I (PubMed:15250827)

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (4)
Respiratory electron transportComplex I biogenesisMitochondrial translation terminationMitochondrial protein degradation
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (5)
mitochondrial diseaseMELAS syndromematernally-inherited Leigh syndromeMERRF syndrome
HGNC:7461UniProt:P03915
MT-CO1Cytochrome c oxidase subunit 1Candidate gene tested inDesconhecido
FUNÇÃO

Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over t

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (6)
Cytoprotection by HMOX1Respiratory electron transportTP53 Regulates Metabolic GenesComplex IV assemblyMitochondrial translation termination
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (6)
mitochondrial diseaseMELAS syndromemitochondrial complex IV deficiency, nuclear-typemitochondrial non-syndromic sensorineural hearing loss
HGNC:7419UniProt:P00395
NDUFS2NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrialDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:22036843, PubMed:28031252, PubMed:30922174). Essential for the catalytic activity of complex I (PubMed:22036843, PubMed:30922174). Essential for the assembly of complex I (By similarity). Redox-sensitive, critical component of the oxygen-sensing pathway in the pulmonary vasculature w

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (2)
Respiratory electron transportComplex I biogenesis
MECANISMO DE DOENÇA

Mitochondrial complex I deficiency, nuclear type 6

A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN6 transmission pattern is consistent with autosomal recessive inheritance.

EXPRESSÃO TECIDUAL(Ubíquo)
Músculo esquelético
154.5 TPM
Ovário
130.0 TPM
Cérebro - Hemisfério cerebelar
124.7 TPM
Coração - Ventrículo esquerdo
120.8 TPM
Cerebelo
120.6 TPM
OUTRAS DOENÇAS (4)
mitochondrial complex I deficiency, nuclear type 6Leber-like hereditary optic neuropathy, autosomal recessive 2mitochondrial complex I deficiencyLeber hereditary optic neuropathy
HGNC:7708UniProt:O75306
MT-ND4NADH-ubiquinone oxidoreductase chain 4Disease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:15250827, PubMed:8344246, PubMed:8644732). Essential for the catalytic activity and assembly of complex I (PubMed:15250827, PubMed:8344246, PubMed:8644732)

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (3)
Respiratory electron transportComplex I biogenesisMitochondrial translation termination
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (6)
mitochondrial diseasematernally-inherited Leigh syndromeMELAS syndromeLeber plus disease
HGNC:7459UniProt:P03905
MT-ND4LNADH-ubiquinone oxidoreductase chain 4LDisease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:28844695). Part of the enzyme membrane arm which is embedded in the lipid bilayer and involved in proton translocation (PubMed:28844695)

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (1)
Mitochondrial translation termination
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (1)
Leber hereditary optic neuropathy
HGNC:7460UniProt:P03901
MT-ND1NADH-ubiquinone oxidoreductase chain 1Disease-causing germline mutation(s) inDesconhecido
FUNÇÃO

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:1959619). Essential for the catalytic activity and assembly of complex I (PubMed:1959619, PubMed:26929434)

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (4)
Respiratory electron transportComplex I biogenesisMitochondrial translation terminationMitochondrial protein degradation
MECANISMO DE DOENÇA

Leber hereditary optic neuropathy

A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

OUTRAS DOENÇAS (5)
mitochondrial diseaseMELAS syndromemitochondrial complex I deficiencymaternally-inherited Leigh syndrome
HGNC:7455UniProt:P03886

Medicamentos e terapias

CYCLOSPORINEPhase 2

Mecanismo: Cyclophilin A modulator

Ver mais no OpenTargets

Variantes genéticas (ClinVar)

169 variantes patogênicas registradas no ClinVar.

🧬 MT-CYB: NC_012920.1(MT-CYB):m.15041G>A ()
🧬 MT-CYB: NC_012920.1:m.8944_15057del ()
🧬 MT-CYB: Single allele ()
🧬 MT-CYB: NC_012920.1(MT-CYB):m.15215G>A ()
🧬 MT-CYB: NC_012920.1(MT-CYB):m.10950_15540del ()
Ver todas no ClinVar

Classificação de variantes (ClinVar)

Distribuição de 2 variantes classificadas pelo ClinVar.

2
Patogênica (100.0%)
VARIANTES MAIS SIGNIFICATIVAS
DNAJC30: NM_032317.3(DNAJC30):c.293A>C (p.Tyr98Ser) [Likely pathogenic]
DNAJC30: NM_032317.3(DNAJC30):c.152A>G (p.Tyr51Cys) [Pathogenic/Likely pathogenic]

Diagnóstico

Os sinais que médicos procuram e os exames que confirmam

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Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Pipeline de tratamentos
Pipeline regulatório — de medicamentos já aprovados a drogas em pesquisa exploratória.
3Fase 36
2Fase 26
1Fase 12
·Pré-clínico7
Medicamentos catalogadosEnsaios clínicos· 1 medicamento · 20 ensaios
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Onde tratar no SUS

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🇧🇷 Atendimento SUS — Neuropatia óptica hereditária de Leber

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Publicações mais relevantes

Timeline de publicações
509 papers (10 anos)
#1

Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.

Investigative ophthalmology &amp; visual science2026 Feb 02

The Vglut2-Cre;ndufs4loxP/loxP mouse strain with retinal ganglion cell (RGC)-specific mitochondrial complex I dysfunction develops severe RGC degeneration by postnatal day 90 (P90), with accompanying retinal mononuclear phagocyte (MNP) accumulation. We have reported that continuous exposure to hypoxia partially rescues RGC death in these mice, with minimal effect on MNP abundance. We hypothesized that pharmacological depletion of MNPs with the colony-stimulating factor-1 receptor inhibitor pexidartinib would enhance RGC neuroprotection by hypoxia. Iba1+ retinal MNP depletion was assessed in C57Bl/6J mice fed control or pexidartinib-infused chow beginning at P25. Subsequently, Vglut2-Cre;ndufs4loxP/loxP mice and control littermates were raised under normoxia or hypoxia and fed control or pexidartinib chow from P25 to P90. The neuroprotective effect of pexidartinib and hypoxia alone and in combination was assessed by quantifying RGC soma and axon survival in retinal flat mounts and optic nerve cross-sections. Pexidartinib completely depleted retinal MNPs within 1 week of treatment. Untreated Vglut2-Cre;ndufs4loxP/loxP mice exhibited the expected approximately 50% reduction of RGC soma and axon survival at P90 (P < 0.0001 for both). Hypoxia or pexidartinib monotherapy each reduced RGC degeneration by more than one-half, whereas their combination resulted in complete RGC neuroprotection (P < 0.01 for all 3 treatments). Normal myelination patterns were restored in mice receiving dual therapy. Pexidartinib effectively depletes retinal MNPs and is neuroprotective in the setting of severe RGC mitochondrial dysfunction. This therapeutic effect is additive to that of hypoxia. Combating retinal neuro-inflammation may therefore be a useful adjunct therapy in mitochondrial optic neuropathies like Leber hereditary optic neuropathy (LHON).

#2

Atypical clinical and MRI features in Leber hereditary optic neuropathy: a case series of four patients.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2026 Jan 02

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder typically presenting with subacute, painless, bilateral vision loss in young individuals. While often recognizable, atypical presentations can complicate diagnosis. Notably, optic nerve lesions on MRI are uncommon in LHON and are typically associated with inflammatory optic neuropathies, increasing the risk of misdiagnosis. We retrospectively analyzed four patients who initially presented with suspected optic neuritis but were later diagnosed with LHON. Demographic, genetic, clinical, and multimodal data were retrieved from medical records. The series included two adolescent males, a 51-year-old man, and a 52-year-old woman. All experienced subacute, bilateral vision loss and were later found to carry pathogenic LHON mutations. However, their initial presentations were misleading. The two adult patients presented beyond the typical age of onset; one was initially diagnosed with glaucoma due to increased intraocular pressure, while the other had a history of Fahr's syndrome. One adolescent reported ocular pain with eye movements and showed a relative afferent pupillary defect, mimicking optic neuritis. Two patients lacked typical fundoscopic findings suggestive of LHON. MRI findings further complicated the diagnosis: all patients showed T2-FLAIR hyperintensities of the optic nerves with contrast enhancement, and in three cases abnormalities extended posteriorly to the chiasm and optic tracts on follow-up MRI. MRI abnormalities involving the optic pathway do not exclude LHON and may be present in atypical cases. LHON should be considered in all patients presenting with bilateral subacute visual loss, even when clinical or imaging features suggest alternative diagnoses.

#3

Integrated molecular and clinical profiling of primary mitochondrial oxidative phosphorylation disorders in an Indian cohort: Insights from genetics, neuroimaging, and machine learning.

Mitochondrion2026 Mar 16

Primary mitochondrial disorders are clinically and genetically heterogeneous and remain underdiagnosed in resource-limited settings. We performed a retrospective observational study (March 2016-January 2024) at a tertiary neurology center in Eastern India to characterize the clinical, biochemical, neuroimaging, electrophysiological, and molecular features of suspected mitochondrial disease and to explore interpretable machine-learning approaches for syndromic stratification. Forty-eight patients from 42 unrelated families were classified as MELAS (n = 17), chronic progressive external ophthalmoplegia (CPEO; n = 14), Leber hereditary optic neuropathy (LHON; n = 10), or Leigh syndrome (n = 7). Mean age at presentation was 23.9 years (range: 9 months-60 years), with a slight male predominance. Neuroimaging was abnormal in 23/48 (47.9%) and showed syndrome-concordant patterns, including stroke-like cortical lesions in MELAS and symmetric basal ganglia involvement in Leigh syndrome; brain MRI was typically normal in CPEO. Elevated blood and/or cerebrospinal fluid lactate was common, and electroencephalographic abnormalities were concentrated in MELAS and Leigh syndrome. Targeted molecular testing in a subset identified pathogenic mtDNA variants consistent with phenotype, including MT-TL1 variants in MELAS, m.11778G>A in MT-ND4 in LHON, and m.8993T>G in MT-ATP6 in Leigh syndrome; no mtDNA deletions were detected in tested CPEO cases. Decision tree and random forest models highlighted clinically intuitive discriminators (e.g., visual loss, external ophthalmoplegia/ptosis, and seizure phenotype), supporting their potential role as transparent triage tools for targeted molecular evaluation. This cohort provides the first detailed characterization of mitochondrial syndromes in Eastern India and supports a pragmatic diagnostic framework integrating bedside phenotyping, targeted assays, and interpretable machine learning.

#4

Five-year post-onset visual acuity trajectories in Japanese Leber hereditary optic neuropathy: a longitudinal analysis by age, sex, and mtDNA mutation.

Canadian journal of ophthalmology. Journal canadien d'ophtalmologie2026 Mar 12

To compare 5-year visual acuity trajectories in Leber hereditary optic neuropathy (LHON) by age at onset. A retrospective single-center cohort study. Fifty-seven patients (114 eyes) with genetically confirmed, bilateral-onset LHON. Serial best-corrected visual acuity (BCVA, logMAR) over 5 years was extracted from medical records. The age at onset was grouped as ≤19, 20-49, or ≥50 years. Sex and primary mutation (m.11778G>A vs m.14484T>C) were also assessed. Longitudinal trajectories were analyzed using linear mixed-effects models. Between-group differences were summarized using ΔlogMAR curves, area under the Δ curve (AUCΔ), and model-based probabilities of achieving logMAR ≤1.0. The median age at onset was 30.0 years (range: 8-69): 15 patients (26%) were ≤19 years old, 31 (54%) were 20-49 years old, and 11 (19%) were ≥50 years old. Relative to the 20-49-year reference group, the ≤19-year group had better visual outcomes over 5 years, with a negative AUCΔ and higher probabilities of achieving logMAR ≤1.0 (70.2% vs 13.6% at 60 months). The ≥50-year group showed poorer vision over time, with a positive AUCΔ and low probabilities of recovery. Differences by sex were small. Eyes with m.14484T>C had more favourable Δ trajectories than those with m.11778G>A, although the estimates were imprecise. In this cohort, onset at ≤19 years was associated with earlier and greater visual recovery, whereas onset at ≥50 years was associated with persistently worse vision. Age at onset is an important modifier of 5-year visual prognosis in bilaterally affected LHON.

#5

Leber Hereditary Optic Neuropathy Caused by the Rare MT-ND1 m.3394T>C Mutation: A Case With Favorable Visual Prognosis and a Literature Review.

Cureus2026 Feb

Leber hereditary optic neuropathy (LHON) is an inherited mitochondrial optic neuropathy characterized by acute or subacute painless central visual loss. Most cases are associated with three primary mitochondrial DNA mutations; however, rare variants remain incompletely characterized. Early diagnosis is essential for appropriate management and genetic counseling. We report the case of a 51-year-old Lithuanian woman who presented with painless, progressive central visual loss. Initial neurological and ophthalmological investigations were unremarkable, and corticosteroid therapy was ineffective. Genetic testing revealed a rare homoplasmic m.3394T>C mutation in the MT-ND1 gene. The patient was subsequently treated with idebenone and followed for six years. Following initiation of idebenone therapy, the patient demonstrated gradual and sustained improvement in best-corrected visual acuity, reaching 1.0 in both eyes. Visual fields stabilized, and long-term follow-up showed preserved visual function. Optical coherence tomography revealed persistent but stable structural changes, including retinal nerve fiber layer and ganglion cell layer thinning in the affected eye. This case highlights the potential for favorable long-term visual outcomes in patients with LHON associated with rare mitochondrial variants. It underscores the importance of considering hereditary optic neuropathy in patients with painless visual loss and poor response to corticosteroids. Further studies are needed to clarify genotype-phenotype correlations and treatment responsiveness in rare LHON-associated mutations.

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Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
2024

Leber Hereditary Optic Neuropathy 3 Weeks After COVID-19 Vaccination.

Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
2023

Changes in visual acuity using low vision devices in patients with Leber hereditary optic neuropathy: A retrospective study.

Indian journal of ophthalmology
2022

Case Report: Abnormalities of sperm motility and morphology in a patient with Leber hereditary optic neuropathy: Improvement after idebenone therapy.

Frontiers in neurology
2023

Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups.

International journal of molecular sciences
2023

Psychometric Validity of the Visual Function Index in Leber Hereditary Optic Neuropathy.

Translational vision science &amp; technology
2023

Leber Mitochondrial Optic Neuropathy in Pediatric Females With Focus on Very Early Onset Cases.

Journal of child neurology
2022

Clinical Profile of Patients with Leber Hereditary Optic Neuropathy (LHON): An Ambispective Study of North Indian Cohorts.

Annals of Indian Academy of Neurology
2024

Cognitive Impairment in Phenotypic Leber Hereditary Optic Neuropathy Caused by Mutation in Nuclear Gene NDUFAF5.

Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
2023

Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?

American journal of human genetics
Ver todos os 558 no EuropePMC

Associações

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Comunidades

Grupos ativos de quem convive com esta doença aqui no Raras

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Doenças relacionadas

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Referências e fontes

Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.
    Investigative ophthalmology &amp; visual science· 2026· PMID 41626869mais citado
  2. Atypical clinical and MRI features in Leber hereditary optic neuropathy: a case series of four patients.
    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology· 2026· PMID 41483035mais citado
  3. Integrated molecular and clinical profiling of primary mitochondrial oxidative phosphorylation disorders in an Indian cohort: Insights from genetics, neuroimaging, and machine learning.
    Mitochondrion· 2026· PMID 41850596mais citado
  4. Five-year post-onset visual acuity trajectories in Japanese Leber hereditary optic neuropathy: a longitudinal analysis by age, sex, and mtDNA mutation.
    Canadian journal of ophthalmology. Journal canadien d'ophtalmologie· 2026· PMID 41833325mais citado
  5. Leber Hereditary Optic Neuropathy Caused by the Rare MT-ND1 m.3394T&gt;C Mutation: A Case With Favorable Visual Prognosis and a Literature Review.
    Cureus· 2026· PMID 41822676mais citado
  6. Leber Hereditary Optic Neuropathy in the Elderly: A Case Report.
    Case Rep Ophthalmol· 2026· PMID 41938630recente
  7. Leber hereditary optic neuropathy triggered by the AstraZeneca coronavirus disease 2019 vaccination.
    Oman J Ophthalmol· 2026· PMID 41930030recente
  8. Impact of individualized colored spectacle filters on photophobia and visual comfort in central visual field defect patients: a one-year study.
    Sci Rep· 2026· PMID 41888298recente
  9. Chronic Progressive External Ophthalmoplegia Associated With the m.14484T>C Leber Hereditary Optic Neuropathy Mutation.
    J Neuroophthalmol· 2026· PMID 41870410recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:104(Orphanet)
  2. OMIM OMIM:535000(OMIM)
  3. MONDO:0010788(MONDO)
  4. GARD:6870(GARD (NIH))
  5. Variantes catalogadas(ClinVar)
  6. Busca completa no PubMed(PubMed)
  7. Artigo Wikipedia(Wikipedia)
  8. Q1262161(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar

Neuropatia óptica hereditária de Leber
Compêndio · Raras BR

Neuropatia óptica hereditária de Leber

ORPHA:104 · MONDO:0010788
Prevalência
1-9 / 100 000
Herança
Mitochondrial inheritance
CID-10
H47.2 · Atrofia óptica
CID-11
Ensaios
9 ativos
Medicamentos
1 registrados
Início
Adolescent, Adult
Prevalência
2.6 (Netherlands)
MedGen
UMLS
C0917796
Repurposing
1 candidato
idebenonecalcium channel modulator
EuropePMC
Wikidata
Wikipedia
Papers 10a
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