Leber hereditary optic neuropathy (LHON): mitochondrial DNA and sight loss

LHON affects the optic nerve, the bundle of fibres that carries visual signals from the eye to the brain. Fight for Sight describes sudden, painless loss of central vision, with progression over days, weeks or months rather than being instant, and says complete blindness is not usual, since peripheral vision is preserved even in severe cases. The NHS Genomics Education Programme adds that central vision falls to a level often described as hand movements only, colour vision is lost and the visual field shows a dense central blind spot.

Typically one eye is affected first and the second follows within months. The Lily Foundation says that in around a quarter of cases the onset of vision loss occurs in both eyes at the same time, and that most patients first notice problems between 15 and 35. Early on, the optic nerve may look normal in nearly one in five people at diagnosis, which is one reason genetic testing is important.

Some people also have features outside the eye. The programme notes reports of tremor, peripheral neuropathy, a multiple-sclerosis-like illness and heart rhythm problems, so cardiology or neurology referral may be advised.

Mitochondria are the energy-producing structures inside cells, and they carry a small circle of their own DNA. Retinal ganglion cells that make up the optic nerve have very high energy demands, so they are especially vulnerable when mitochondria do not work properly, Fight for Sight explains. The NHS Genomics Education Programme says three common point changes in mitochondrial genes account for approximately 90% of cases, in the genes MT-ND1, MT-ND4 and MT-ND6, and that other changes in mitochondrial genes, and rarely nuclear genes, have been found.

The programme describes the outlook for sight as varying by change: the MT-ND4 variant is the commonest, present in 60% to 70% of affected people of Northern European descent and about 90% of those of Asian descent, with a poorer chance of partial recovery, while the MT-ND6 variant is the most common among people of French Canadian descent and has a better chance of recovery (37% to 65%). The Lily Foundation says the MT-ND4 change accounts for over 60% of cases in the UK. Specific nucleotide notation varies between sources, so a laboratory report is the reliable way to check an individual result.

Mitochondria come from the egg, not the sperm. Fight for Sight says a mother who carries the genetic fault will pass it on to all her children, but a father cannot pass it on. The NHS Genomics Education Programme calls this maternal inheritance and says a rare form caused by variants in nuclear DNA follows the autosomal recessive pattern instead, with a 1 in 4 chance of an affected child when both parents are carriers.

What surprises families is how many carriers never lose vision. The programme says about 50% of males and 90% of females with primary LHON-causing mtDNA variants do not develop blindness, so most people with these variants remain symptom-free, and Fight for Sight puts it the other way: about 50% of men and 10% of women who carry a mutation will be affected. The programme notes that penetrance varies markedly between family branches, and that only about 60% of families with this form report visual loss among maternal relatives.

The median age of onset is between 20 and 30, but vision loss can happen at any age. Someone who remains well after that age has a falling risk each year, and over 90% of carriers who lose vision do so before 50. Smoking and heavy alcohol use, especially binge drinking, are associated with a higher chance of vision loss, according to the programme and the Lily Foundation. A LHON-causing variant does not predict whether, when or how severely a person will lose vision.

Genetic testing looks for the common mitochondrial changes first and then for rarer ones if needed. The NHS Genomics Education Programme notes that prenatal testing and pre-implantation genetic testing are both possible for people at increased risk, but both need caution because a positive prenatal result can be misinterpreted: the proportion of mitochondrial DNA carrying the change in the sample may differ from that in the rest of the baby.

The programme records that the first UK licence for mitochondrial donation was approved by the Human Fertilisation and Embryology Authority in 2017, a technique intended for mothers with variants in mitochondrial DNA. Women who carry a LHON change can ask a clinical genetics service which options apply to them.

The NHS Genomics Education Programme says management has been supportive, including assistive aids, occupational rehabilitation and registration of sight loss through the certificate of visual impairment. It recommends advising affected people not to smoke and to avoid excessive alcohol, and it considers it reasonable to avoid activities with a risk of head trauma, industrial toxins and drugs with mitochondrial toxic effects.

On medicines, the programme says idebenone received authorisation in Europe under exceptional circumstances for adolescents and adults. The Lily Foundation says NICE approved idebenone for people aged 12 and over in England in August 2025, with availability expected from early 2026, and notes that not every patient will benefit and that results vary. Gene therapy for the commonest change remains experimental, according to the programme, and has not yet been recommended by major regulators. Availability and eligibility change, so a neuro-ophthalmology team is the right source for the present position.