Hereditary optic atrophy

Beminger, T.A., L.V. Meyer, E. Siess, O. Schon, and F.D. Goebel. 1989. Leber s hereditary optic atrophy further evidence for a defect of cyanide metabolism Brit. Jour. Ophthalmol. 73 314-316. 

The nervous system is the most sensitive target for cyanide toxicity, partly because of its high metabolic demands. High doses of cyanide can result in death via central nervous system effects, which can cause respiratory arrest. In humans, chronic low-level cyanide exposure through cassava consumption (and possibly through tobacco smoke inhalation) has been associated with tropical neuropathy, tobacco amblyopia, and Leber s hereditary optic atrophy. It has been suggested that defects in the metabolic conversion of cyanide to thiocyanate, as well as nutritional deficiencies of protein and vitamin B12 and other vitamins and minerals may play a role in the development of these disorders (Wilson 1965). 

Persons with a metabolic disturbance in the conversion of cyanide to thiocyanate may be at greater risk. A defect in the rhodanese system and vitamin B12 deficiency have been associated with tobacco amblyopia and Leber s hereditary optic atrophy in persons exposed to cyanide in tobacco smoke (Wilson 1983). 

WilsonJ. 1965. Leber s hereditary optic atrophy A possible defect of cyanide metabolism. Clin Sci 29 505-515. 

The clinical symptoms of mitochondrial diseases are highly varied and include seizures, vomiting, deafness, dementia, stroke-like episodes, and short stature. Although there are many types of mitochondrial disorders, four of the most common types are as follows Kearns-Sayre syndrome, Leber s hereditary optic atrophy, MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) and MERRE (myoclonic epilepsy with ragged red fibres). 

Dominant optic atrophy [13, 14] The most prevalent hereditary optic atrophy resulting in a progressive loss of visual acuity, centro-cecal scotoma and bilateral temporal atrophy of the optic nerve. It has been ascribed to mutations in the OPA1 gene encoding a dynamin-related protein localized to mitochondria. Anomalies of mitochondrial integrity and distribution are suspected to result from impairment of protein function. 

Figure 47.3 Cyanocobalamin fraction in uremia and neuro-ophthalmological diseases. The fraction ratio of cyanocobalamin was as extremely high as 10.5 2.6%, which is equivalent to the ratio (10.4 5.2%) observed in patients with Leber s disease. Patients with Leber s disease have an inborn error in cyanide metabolism and are unable to detoxify cyanide to thiocyanate (Wilson 1965a). Leber s disease is a hereditary optic atrophy. The onset and severity of Leber s disease is related to the pattern of smoking in many patients (Wilson 1965a, 1965b).

Wilson, J., 1965b. Leber s hereditary optic atrophy. Some clinical and etiological consideration. Brain. 86 347-362. 

Abnormalities suggestive of deranged cyanide emd vitamin Bi2 metabolism have been demonstrated in Leber s disease (hereditary optic atrophy) and in dominantly inherited optic atrophy, and consist of significant elevations of pleisma cyanocobalamin [56]. Similar changes have been reported in sporadic cases of bilateral optic atrophy occurring in Europeans, and in cases of so-called tobacco amblyopia. 

Complex I deficiency due to mtDNA mutations (seven subunits of complex I are encoded by mtDNA) can be divided into encephalomyopathies and myopathies. The most important encephalomyopathy is Leber s hereditary optic neuropathy, characterized by acute or subacute loss of vision due to severe bilateral optic atrophy, with onset usually between 18 and 30 years and marked predominance in men. Three mutations (in ND1, ND4 and ND6)... 

Optic nerve atrophy Patients with early Leber disease (hereditary optic nerve atrophy) treated with cyanocobalamin suffer severe and swift optic atrophy. 

Contraindications Folic acid deficiency anemia, hereditary optic nerve atrophy, history of allergy to cobalamins... 

Leber s hereditary optic neuropathy (Leber optic atrophy)... 

MS), which is a demyelinating disorder. When optic neuritis occurs without disc swelling, the condition is called retrobulbar neuritis. When disc swelling is associated with optic neuritis, the condition is called papillitis. Papilledema is bilateral disc edema associated with increased intracranial pressure OCP). Optic atrophy, the end stage of many optic neuropathies, is characterized by a pale disc and associated with a relative afferent pupillary defect (RAPD) and possible loss of visual acuity, color vision, and visual field. One example of disc atrophy occurs in cases of Leber s hereditary optic neuropathy... 

LHON (Leber hereditary optic neuropathy) Late onset, acute optic atrophy. 90% of European and Asian cases result from mutation in NADH dehydrogenase. 

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