Leber Hereditary Optic Neuropathy (LHON).
Incidence
Maternally inherited disease. 18% of fem carriers are affected. 50-100% of sons of fem carriers are affected. 70-100% daugthers of female carriers are carriers. 85% of affected pts are males (? reasons). At least 15 mtDNA point mutations are described.
Clinical Characteristics
Symptoms usually start at adolescence or young adulthood (usually between 18-25 yrs of age), but can be seen as young as 5 yrs. or as old as 60 yrs. There is sudden onset of visual loss, usually bilateral but may start unilateral and then become bilateral some weeks to months later. Duration of progress is approx. 4 months. Visual acuity is < 20/200 in 98%. Visual loss progress from enlarged blind spot to large centrocaecal scotoma. Optic fundi show characteristic papilledema and tortuosity of retinal vessels (only arteries, veins are normal). Retinal changes occur in 50%. Vision may improve with time. There is retinal degeneration. There is telangiectatic microangiopathy around the papilla. VEP are decreased and then absent. Approx. 2/3 of pts have abnormal AEP. Some pts may have neurological symptoms such as ataxia, choreoathetosis, pyramidal signs, peripheral neuropathy, psychiatric disorders (such as affective disorder and irritability) and cardiac dysrrhythmias. If condition start in childhood, may have acute neurological deficit and bone changes like kyphosis and spondyloepiphyseal dysplasia. Muscle biopsy (light microscopy) is normal. Muscle biopsy may show on EM aggregates of enlarged mitochondria in the subsarcolemmal region. Blood and CSF lactate is normal. MRI may have bilateral striatal (putamen) lucencies (usually associated with dystonia) and at times is seen in relatives without ocular signs.
Precipitants
unknown.
Provocation Tests
no
Diagnostic Procedures
DB-W. Muscle biopsy may show on EM aggregates of enlarged mitochondria in the subsarcolemmal region. VEP are decreased and then absent. Approx. 2/3 of pts have abnormal AEP.