Leberova nasljedna opticka neuropatija

Leber hereditary optic neuropathy (LHON) is characterized by bilateral, painless, subacute visual failure
that develops during young adult life. Males are four to five times more likely than females to be affected.
Affected individuals are usually entirely asymptomatic until they develop visual blurring affecting the
central visual field in one eye; similar symptoms appear in the other eye an average of two to three
months later. In about 25% of cases, visual loss is bilateral at onset. Visual acuity is severely reduced to
counting fingers or worse in the majority of cases, and visual field testing shows an enlarging dense
central or centrocecal scotoma. After the acute phase, the optic discs become atrophic. Significant
improvements in visual acuity are rare and most persons qualify for registration as legally blind (visual
acuity 20/200). Neurologic abnormalities such as postural tremor, peripheral neuropathy, nonspecific
myopathy, and movement disorders have been reported to be more common in individuals with LHON
than in controls. Some individuals with LHON, usually women, may also develop a multiple sclerosis
(MS)-like illness.
The diagnosis is based on ophthalmologic findings. Testing includes dilated fundus examination to
identify characteristic optic disc and vascular changes in the acute phase; kinetic (Goldmann) or static
perimetry to delineate the characteristic central or centrocecal scotoma; electrophysiologic studies in
selected cases (visual evoked potentials to confirm optic nerve dysfunction and pattern electroretinogram
to confirm the absence of retinal disease); and neuroimaging to exclude compressive, infiltrative, and
inflammatory causes of a bilateral optic neuropathy.
Treatment of manifestations: Management of affected individuals is largely supportive, with the provision
of visual aids, help with occupational rehabilitation, and registration with the relevant social services.
ECG may reveal a pre-excitation syndrome in individuals harboring mtDNA LHON-causing mutations,
but no further intervention is required in the absence of cardiac symptoms. A multidisciplinary approach
to those affected individuals with extra-ocular neurologic features (ataxia, peripheral neuropathy and
dystonia) should be considered to minimize the functional consequences of these complications
Leberova opticka neuropatija prva je bolest u ljudi za koju se pokazalo da je uzrokovana tockastim
mutacijama mtDNA , najcesca mutacija je u nukleotidu m.11778i nalazi se u 70% bolesnika .
Leber hereditary optic neuropathy is caused by mutations in mtDNA and it is transmitted by maternal
inheritance
The mother of a proband usually has the mtDNA mutation and may or may not have symptoms. In most
cases a history of visual loss affecting maternal relatives at a young age is present, but up to 40% of cases
are simplex (i.e., occur in a single individual in a family). A male (affected or unaffected) with a primary
LHON-causing mtDNA mutation cannot transmit the mutation to any of his offspring. A female (affected
or unaffected) with a primary LHON-causing mtDNA mutation transmits the mutation to all of her
offspring. Prenatal diagnosis for mitochondrial mutations is possible if the disease-causing mutation in a
family is known; however, accurate interpretation of a positive prenatal test result is difficult because the
mtDNA mutational load in amniocytes and chorionic villi may not correspond to that of other fetal or

adult tissues, and the presence of the mtDNA mutation does not predict the occurrence of disease, age of
onset, severity, or rate of disease progression. Prenatal testing may be available through laboratories
offering testing for the gene of interest or custom testing.
Clinical Diagnosis