In this section:

How is LHON diagnosed?
Importance of early diagnosis
Symptom tracker 
Who to talk to?
Diagnosis challenges

How is LHON diagnosed?

LHON is a clinical diagnosis and can be confirmed only through a genetic test that can identify the mutation.Footnote1 In addition to this, patients can often provide a history of visual loss in family members.Footnote2

Some of the recommended tests for LHON diagnosis include:Footnote1

  • An eye examination
  • An optical coherence tomography (OCT) scan to measure the retinal
    ganglion cells (RGCs) and retinal nerve fibre layer (RNFL) alterations
  • A pattern electroretinogram (PERG) to measure the electrical responses in the eyeFootnote3
  • A visual field test to measure the area of central vision loss
  • An MRI or CT scan to rule out inflammation in the eye and central nervous system lesionsFootnote1,Footnote4

Importance of early
diagnosis

If you are experiencing problems with your eyesight, such as sudden blurring or clouding in the centre of your vision, do not wait to see if it gets worse.Footnote1 In particular, patients with LHON are often young adults with preserved peripheral vision, who make excellent candidates for low vision rehabilitation.Footnote5

Since LHON is a rare disease, it’s often misdiagnosed, resulting in diagnosis delays

Eye testing

Who to talk to?

Look for an LHON specialist such as an ophthalmologist at the earliest opportunity. Talk to your GP about your concerns around LHON to help with the diagnosis. They can refer you to an eye care specialist for further management of your condition.6

If you have a confirmed LHON diagnosis, you can request to be seen by a neuro-ophthalmologist. They are specialists who understand LHON.6

Take urgent action by visiting an ophthalmologist on the first signs of LHON

Genetic testing for LHON

If your consultant suspects LHON, after examining your family history and conducting ophthalmologic, extraocular and neuroimaging tests, you could be advised to take genetic testing to confirm a diagnosis.Footnote1

Targeted mtDNA analysisFootnote1,7

This involves targeted testing for three of the most common mitochondrial DNA point mutations, where 90% of the cases are identified.

If targeted testing doesn’t yield a positive result, a multigene panel test could identify rarer mutations in the most commonly affected genes.1

Multigene panel testFootnote1,8

If a targeted mtDNA analysis doesn’t give you a confirmation, a multigene panel test would be the next step. This test helps increase the chance of identifying if you have LHON at a reasonable cost.

Mitochondrial sequencingFootnote1,7,9

If suspicion of LHON remains high, you could be referred to
specialist centres for a full mitochondrial sequencing.

Nuclear-mitochondrial gene screeningFootnote9,10

To determine if you have a rare autosomal recessive mode of inheritance for LHON (arLHON), you may also be referred to a nuclear-mitochondrial gene screening to test the nuclear gene (DNAJC30) involved in mitochondrial maintenance.

Find out if you have relatives in your family with vision loss

Take urgent action by visiting an ophthalmologist on the first signs of LHON

Genetic counselling1

Genetic counselling in LHON is difficult because nothing can predict if, when or how severely it can affect a carrier. If the mother has one of the LHON mutations, all her children will inherit it. It will be passed on to the children by mothers and not by fathers.

If you plan to be a mother and have a family history of LHON, you might want to consider taking a prenatal test to determine the genetic risk. Information from your genetic counselling can help you make your family planning decisions.

If you or a family member is diagnosed with LHON, it’s important to share the diagnosis with the maternal side of your family.1 The risk to other family members depends on the genetic status of the mother: if the patient’s mother has the mtDNA pathogenic variant, her siblings and her mother are at risk as well.Footnote1

While ongoing observation of symptoms are not necessary in asymptomatic individuals with an LHON-causing mtDNA, they should seek immediate medical attention if they experience any issues with their vision.Footnote1 It is also worth making them aware of the potential risk factors and triggers.

Information from your genetic counselling can help you make your family planning decisions.

Find out if you have relatives in your family with vision loss

Symptom tracker 

 

Keep track of how your symptoms are progressing.

Download our symptom tracker

Diagnosis challenges

The journey to an LHON diagnosis can be long and frustrating. LHON is such a rare genetic condition that even the most experienced doctors may have never seen someone in their practice.Footnote11 People with LHON are often treated for other causes of vision loss first before being diagnosed with LHON.Footnote11

Doctors will look at a person’s medical history, symptoms, physical exam, and genetic test results to confirm a diagnosis.Footnote1

Knowing about LHON can speed up your diagnosis

  • Autosomal recessive inheritance: This is one of the ways a genetic trait or condition can be passed down from parent to child. In autosomal recessive inheritance, the affected individual inherits one copy of a mutated gene from each parent for a genetic condition to occur.Footnote10,12

    DNA: This is the hereditary material located inside the cells in our body and contains the information needed for that cell, and our body, to develop and function. This information is passed from parents to their children through DNA.Footnote12

    Maternal inheritance: When a mutation is passed from mothers, but not from fathers, to their children.Footnote12

    Mitochondria: Small structures (organelles) that exist inside our cells and generate the energy needed for that cell to function.Footnote12,13

    Mitochondrial DNA (mtDNA): DNA that is found in the mitochondria.Footnote12

    Mitochondrial sequencing: A technique which can help analyse mitochondrial DNA and identify disease-related mutations which could be missed by other methods.Footnote1,12

    Mutations: The genes in our body act as instructions to make molecules called proteins. Changes in a gene are called mutations. These prevent one or more of the proteins to do their jobs causing disease.Footnote12

    Nuclear gene: A gene which is found in the cell nucleus.Footnote12

    Nucleus: The structure inside our cells which contains most of our DNA.Footnote12

    Optic nerve: The nerve that carries visual information from the retina to the brain.Footnote14

    Organelles: Organelles are special structures within a cell that perform various jobs that are crucial to a cell.Footnote15

    Pathogenic variant: This refers to a mutated gene that increases an individual’s chance of developing a specific disease or disorder.Footnote1,12

    Point mutations: Mutations where a single nucleotide base (the building blocks of DNA) is changed, inserted or deleted from the DNA sequence.Footnote10,16

    Retinal ganglion cells: These are cells that connect the inner retina of the eye to the brain. Together, these cells form the optic nerve.Footnote14

    Retinal nerve fibre layer: A specific layer of the retina composed primarily of retinal ganglion cells.Footnote14

    1. Yu-Wai-Man P and Chinnery PF. Leber Hereditary Optic Neuropathy. GeneReviews® [Internet]. 2021. Available at: https:// www.ncbi.nlm.nih.gov/books/NBK1174/. Accessed: March 2023.

    2. Sadun A, et al. Curr Treat Options Neurol. 2011;13(1):109–17.

    3. Asanad S and Karanjia R. StatPearls Publishing; 2021. PMID: 32809476.

    4. Man PYW, et al. J Med Genet 2002;39:162–9.

    5. Theodorou-Kanakari A, et al. Adv Ther. 2018;35:1510–18.

    6. Carelli V, et al. Hum Mol Genet. 2017:26;139–50.

    7. NHS England. National Genomic Test Directory. Testing Criteria for Rare and Inherited Disease. June 2023. Available at: https://www.england.nhs.uk/wp-content/uploads/2018/08/Rare-and-inherited-disease-eligibility-criteria-version-5.2.pdf. Accessed: June 2023.

    8. Genomics England PanelApp. Available at: https://panelapp.genomicsengland.co.uk/panels/530/. Accessed: March 2023.

    9. NHS Commissioning Board, 2013. Rare mitochondrial disorders service (all ages). Service specification 13/S(HSS)/h.

    10. Stenton SL, et al. J Clin Invest. 2021:15;131(6):e138267.

    11. Carelli V, et al. Eur Ophthalmic Rev. 2019;13 (Suppl 2).

    12. Genetic Alliance. The New York-Mid-Atlantic Consortium for Genetic and Newborn Screening Services. Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2009. Available at: https:// www.ncbi.nlm.nih.gov/books/NBK115558/. Accessed: March 2023.

    13. Meyersen C, et al. Clin Ophthal. 2015;9:1165–76.

    14. Carelli V, et al. Biochim Biophys Acta. 2009;1787(5):518–28.

    15. Heald R and Cohen-Fix O. Curr Opin Cell Biol. 2014;26:79–86.

    16. Abdullah T, et al. Bioinformation. 2016;12(3):98–104.

Disclaimer: The information on this website is intended only to provide knowledge of Leber’s hereditary optic neuropathy (LHON). This information should not be used in place of advice from a healthcare professional. Please contact your doctor for advice. This website has been produced by Chiesi Pharmaceuticals. The website has been developed in accordance with industry and legal standards to provide information for the general public about LHON. Chiesi Pharmaceuticals makes every reasonable effort to include accurate and current information. However, the information provided in this website is not exhaustive.