Those who are not aware of any family members with LHON are taken by surprise when they suddenly lose central vision, and usually struggle to identify the cause. Since LHON is so rare, the medical community usually suspects, tests for, and treats other causes of sudden vision loss. An MRI may be conducted to rule out a brain tumor and to view any optic nerve swelling. Since there is no visible damage to the eye or brain, there may be a diagnosis of Functional or Non-Organic Vision Loss which suggests a psychological component, an upsetting misdiagnosis since the vision loss is quite real. It's helpful to see a neuro-ophthalmologist, who is trained and equipped to assess the optic nerves.
Since vision loss usually begins in just one eye, a tentative diagnosis of Optic Neuritis is often made and steroid treatment may be prescribed. Optic Neuritis involves eye pain about 90% of the time while LHON onset is painless, which can help in differentiating LHON from Optic Neuritis. Optic Neuritis usually involves just one eye while LHON usually affects both eyes, so when loss of vision in the second eye begins it may cause the Optic Neuritis diagnosis to be questioned. Testing for Neuromyelitis Optica (NMO) and other possible causes of sudden, bilateral, painless loss of central vision, as well as genetic testing for LHON, may be initiated.
A genetic test usually determines if someone carries an LHON mutation, which confirms the diagnosis. Some labs do a panel test for just the three most common LHON mutations while others include the rare LHON mutations on their panel test. Comprehensive testing of the mitochondrial genome identifies rare LHON mutations. This video provides an overview of various approaches to LHON genetic testing.
When a family member has obtained genetic test results, it can usually be assumed that everyone on the maternal bloodline carries the same mutation with no additional testing, especially if all the mitochondria have the LHON mutation (homoplasmy). In some cases there is a desire to confirm that a maternal relative has a LHON mutation, especially when the genetic test reveals a mix of normal and mutated mitochondria (heteroplasmy). Rather than repeating the panel test or the comprehensive mitochondrial test, a more targeted and less expensive option (Known Familial Mutation test) tests for just the specific mutation already identified in a maternal relative. Because there is usually a clear pattern of genetic inheritance when an LHON mitochondrial mutation has been identified, those with a family member on the maternal inheritance bloodline with an LHON mutation should expect that any sudden, painless central vision loss they experience is likely caused by LHON and quickly have an examination of the optic nerves for confirmation.
When LHON vision loss begins in childhood, the onset may be different from the typical pattern of sudden onset in both eyes, making it particularly difficult to diagnose. Vision loss may be gradual, and perhaps in just one eye. In very young children it may be diagnosed as amblyopia or strabismus, rather than as LHON.