Leber Hereditary Optic Atrophy (Leber's Hereditary Optic Neuropathy)

A maternally linked genetic disorder that presents in mid-life as acute or subacute central vision loss leading to central scotoma and blindness. The disease has been associated with missense mutations in the mtDNA, in genes for Complex I, III, and IV polypeptides, that can act autonomously or in association with each other to cause the disease. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim/, MIM#535000 (April 17, 2001))

Also Known As:

Networked: 605 relevant articles (7 outcomes, 41 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Friedreich Ataxia (Friedreich's Ataxia)
2.	Optic Nerve Diseases (Optic Neuropathy)
3.	Stroke (Strokes)
4.	Lactic Acidosis
5.	Multiple Sclerosis

Experts

1.	Carelli, Valerio: 51 articles (12/2015 - 01/2002)
2.	Sadun, Alfredo A: 23 articles (12/2015 - 01/2002)
3.	Barboni, Piero: 16 articles (02/2014 - 06/2002)
4.	Valentino, Maria Lucia: 15 articles (02/2014 - 06/2002)
5.	Jia, Xiaoyun: 15 articles (01/2013 - 01/2006)
6.	Zhang, Qingjiong: 15 articles (01/2013 - 01/2006)
7.	Yao, Yong-Gang: 15 articles (10/2012 - 01/2007)
8.	Qu, Jia: 13 articles (08/2015 - 03/2005)
9.	Tong, Yi: 13 articles (08/2015 - 09/2002)
10.	Martinuzzi, Andrea: 13 articles (01/2011 - 02/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Leber Hereditary Optic Atrophy:

1.	idebenoneIBA 04/01/2013 - "One trial (idebenone treatment of Leber hereditary optic neuropathy) did not show significant improvement in the primary outcome, but there was significant improvement in a subgroup of patients. " 06/01/2007 - "Despite previous reports of visual recovery with idebenone in patients with LHON, our experience shows that an effective treatment for Leber's disease remains to be found." 05/01/1997 - "Clinical and brain bioenergetics improvement with idebenone in a patient with Leber's hereditary optic neuropathy: a clinical and 31P-MRS study." 06/01/2007 - "To ascertain the efficacy of idebenone and multivitamin treatment in Leber's hereditary optic neuropathy (LHON). " 08/08/1992 - "Remission of Leber's hereditary optic neuropathy with idebenone."
2.	Glutathione (Reduced Glutathione)IBA 02/01/2008 - "Protection against oxidant-induced apoptosis by exogenous glutathione in Leber hereditary optic neuropathy cybrids." 01/01/1984 - "Red cell glutathione has been assayed in a family affected by Leber's optic atrophy. " 01/01/1984 - "Red cell glutathione in Leber's optic atrophy."
3.	AntioxidantsIBA 11/15/2008 - "Antioxidants partially restore glutamate transport defect in leber hereditary optic neuropathy cybrids." 09/15/2013 - "Thus, antioxidants may represent a therapeutic option for MS. The antioxidant idebenone was proven to be beneficial in Friedreich's ataxia and Leber's hereditary optic neuropathy, two disorders caused by mitochondrial alterations. "
4.	Mitochondrial DNA (mtDNA)IBA 10/01/2012 - "[Study on three common mitochondrial DNA mutations in Leber's hereditary optic neuropathy]." 09/01/2011 - "We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. " 01/01/2011 - "Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON). " 09/01/2010 - "To describe the patient profiles of the Leber hereditary optic neuropathy (LHON) Gene Therapy Clinical Trial, year 1. This study aims to identify and characterize affected patients and carriers with the G11778A mutation in mitochondrial DNA for planned gene therapy that will use "allotopic expression" by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. " 09/01/2010 - "The aim of this study was to describe clinical features and search for primary mitochondrial DNA (mtDNA) mutations in 13 unrelated Brazilian patients with Leber's hereditary optic neuropathy (LHON). "
5.	Retinaldehyde (Retinal)IBA 01/01/2005 - "To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in unaffected carriers with Leber's hereditary optic neuropathy (LHON) mutations. " 01/01/2005 - "To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (StratusOCT) in patients with Leber's hereditary optic neuropathy (LHON). " 01/01/2013 - "We assessed retinal ganglion cell (RGC) function, and established a correlation between the neural conduction along the visual pathways and the retinal involvement in Leber's hereditary optic neuropathy (LHON). " 01/01/2013 - "Retinal function and neural conduction along the visual pathways in affected and unaffected carriers with Leber's hereditary optic neuropathy." 11/01/2012 - "Retinal nerve fiber layer thickness variability in Leber hereditary optic neuropathy carriers."
6.	PhosphorusIBA 08/01/1991 - "Leber's hereditary optic neuropathy: genetic, biochemical, and phosphorus magnetic resonance spectroscopy study in an Italian family." 06/01/2002 - "Phosphorus MR spectroscopy shows a tissue specific in vivo distribution of biochemical expression of the G3460A mutation in Leber's hereditary optic neuropathy." 07/01/1995 - "In vivo phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective brain and muscle energy metabolism in three affected siblings in a family with Leber's hereditary optic neuropathy (LHON) with the 11778 mtDNA mutation. " 05/01/1997 - "We used phosphorus magnetic resonance spectroscopy (31P-MRS) to study in vivo brain and muscle bioenergetics in a male patient with Leber's hereditary optic neuropathy (LHON) and mtDNA mutation at 11,778 bp who developed spastic paraparesis with white matter lesions on brain MR imaging. "
7.	Mitochondrial encephalopathyIBA 03/01/2011 - "The aim of this paper is to describe the clinical features and molecular findings of a unique case of Leber's hereditary optic neuropathy (LHON)/mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) overlap syndrome presenting as nonischemic central retinal vein occlusion (CRVO). " 06/01/1991 - "It is argued that this rare disease, since the princeps description in 1964 only reported in England (1986) and the U.S.A (1986), is most likely a singular type of mitochondrial encephalopathy: it is associated with Leber's optic atrophy, and the NMR changes observed have been signalled in other mitochondrial encephalomyelopathies, such as Leigh's disease and MELAS." 04/01/2013 - "These trials have included patients with various mitochondrial disorders, a selected subcategory of mitochondrial disorders, or specific mitochondrial disorders (Leber hereditary optic neuropathy or mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes). " 03/01/1998 - "Mutations usually associated with either mitochondrial encephalopathy, lactic acidosis and stroke-like episode, myoclonic epilepsy with ragged red fibres, or those strongly linked to Leber's hereditary optic neuropathy (LHON) were not detected in patients or controls. " 01/01/2016 - "The screened mutations include A3243G, T3271C and T3291C for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS); A8344G and T8356C for Myoclonus Epilepsy and Rag-Red Fibers (MERRF); G11778A, G3460A and T14484C for Leber's Hereditary Optic Neuropathy (LHON); T8993G/C and T9176G for Leigh syndrome; A1555G for deafness syndrome; G4298A, T10010C, T14728C and T14709C for neuromuscular syndrome. "
8.	NADH DehydrogenaseIBA 11/01/1991 - "This study showed that there is decreased activity of complex I of the respiratory chain in muscle and that cerebral striatal lesions occur in Leber's hereditary optic neuropathy with the NADH-dehydrogenase 4 gene point mutation." 12/01/2013 - "Fifteen novel mutations in the mitochondrial NADH dehydrogenase subunit 1, 2, 3, 4, 4L, 5 and 6 genes from Iranian patients with Leber's hereditary optic neuropathy (LHON)." 05/01/2007 - "G11778A in the subunit ND4 gene of NADH dehydrogenase complex is the most common primary mutation found in Leber's hereditary optic neuropathy (LHON) patients. " 06/01/1991 - "Allelic mutations of the fourth subunit of NADH dehydrogenase are not pathogenetically important in 11778-negative Leber hereditary optic neuropathy." 06/01/1989 - "These mutations have occurred in genes coding for subunits of NADH dehydrogenase, suggesting that a defect of the respiratory chain complex I may cause Leber's disease."
9.	NAD (NADH)IBA 04/01/2014 - "IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. " 02/01/2009 - "Another proband carried homoplasmic mutation 13708G>A (in nicotinamide adenine dinucleotide dehydrogenase subunit 5) that has been associated with Leber's hereditary optic neuropathy. " 05/18/1989 - "A defect in mitochondrial electron-transport activity (NADH-coenzyme Q oxidoreductase) in Leber's hereditary optic neuropathy." 06/01/2004 - "Genetic studies showed that he had a mitochondrial DNA (mtDNA) mutation at position 11778 (within the gene for subunit 4 of NADH-coenzyme Q oxidoreductase), commonly associated with Leber's hereditary optic neuropathy. "
10.	UbiquinoneIBA 01/01/2008 - "Leber hereditary optic neuropathy mutations in the ND6 subunit of mitochondrial complex I affect ubiquinone reduction kinetics in a bacterial model of the enzyme." 05/18/1989 - "A defect in mitochondrial electron-transport activity (NADH-coenzyme Q oxidoreductase) in Leber's hereditary optic neuropathy." 06/01/2004 - "Genetic studies showed that he had a mitochondrial DNA (mtDNA) mutation at position 11778 (within the gene for subunit 4 of NADH-coenzyme Q oxidoreductase), commonly associated with Leber's hereditary optic neuropathy. "

Therapies and Procedures

1.	Plasma Exchange 01/01/1990 - "[Evaluation of the efficacy of plasma exchange in Leber's disease]."
2.	Lasers (Laser) 06/01/1998 - "To study the central retinal nerve fibre layer with scanning laser ophthalmoscopy (SLO) in subjects with Leber's hereditary optic neuropathy (LHON), a disease primarily affecting retinal nerve fibres in the macular area. " 02/01/2014 - "We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. " 12/01/1996 - "Fast capillary electrophoresis-laser induced fluorescence analysis of ligase chain reaction products: human mitochondrial DNA point mutations causing Leber's hereditary optic neuropathy." 06/01/1998 - "Scanning laser ophthalmoscopy as a tool for detecting atrophy of the central retinal nerve fibre layer in Leber's hereditary optic neuropathy."
3.	Intravitreal Injections 12/01/2012 - "The data on the dose and method of intravitreal injection from our study will provide a valuable reference for clinical intravitreal injection of adeno-associated virus-ND4 for the treatment of Leber's hereditary optic neuropathy."
4.	Drug Therapy (Chemotherapy) 11/01/2010 - "The language skills of a male child with Leber hereditary optic neuropathy (LHON) and coincidentally treated for acute lymphoblastic leukemia (ALL) with intrathecal chemotherapy at the age of 3 years 8 months were comprehensively evaluated twice over a 6-month period approximately 5½ years after diagnosis of ALL. " 11/01/2010 - "Language skills in a child with Leber hereditary optic neuropathy following intrathecal chemotherapy for acute lymphoblastic leukemia." 04/01/2003 - "Successful chemotherapy in a male patient with malignant lymphoma and Leber's hereditary optic neuropathy (LHON)."
5.	Bariatric Surgery 03/01/2009 - "Leber hereditary optic neuropathy associated with malabsorption syndrome after bariatric surgery."