Leber’s disease

Bi2 Meat, dairy, eggs, seafood Toxic optic neuropathy Optic nerve atrophy (in Leber s disease)... 

Our findings (Koyama el al. 1996,1997) that the smokers undergoing dialysis have peripheral neuropathy and that the fraction ratio of cyanocobalamin is comparable to that observed in patients with Leber s disease indicate the possibility of cyanide metabolism disorder in patients with CKD. In patients with CKD, thiocyanate (SCN) accumulates due to the decrease in its clearance. It impairs the major metabolic pathway of cyanide and the cyanide pool therefore increases. This increase accelerates cyanide detoxication via cyanocobalamin synthesis using vitamin B12, resulting in an increase in the... 

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).

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. 

Much of the toxicological interest in cyanide relating to mammals has focused on its rapid lethal action. However, its most widely distributed toxicologic problems are due to its toxicity from dietary, industrial, and environmental factors (Way 1981, 1984 Gee 1987 Marrs and Ballantyne 1987 Eisler 1991). Chronic exposure to cyanide is correlated with specific human diseases Nigerian nutritional neuropathy, Leber s optical atrophy, retrobulbar neuritis, pernicious anemia, tobacco amblyopia, cretinism, and ataxic tropical neuropathy (Towill etal. 1978 Way 1981 Sprine etal. 1982 Beminger et al. 1989 Ukhun and Dibie 1989). The effects of chronic cyanide intoxication are confounded by various nutritional factors, such as dietary deficiencies of sulfur-containing amino acids, proteins, and water-soluble vitamins (Way 1981). 

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). 

Indications Alzheimer s dementia, cardiovascular disease, cerebrovascular disease, demyelination, depression, Friedreich s ataxia, improving memory, Leber s hereditary optic neuropathy Category Coenzyme Q10 analog Half-life N/A... 

Mildly deleterious base substitutions 2. Moderately deleterious nucleotide substitutions 3. Severe nucleotide substitutions Familial deafness, Alzheimer s disease, Parkinson s disease Leber s Hereditary Optic Neuropathy (LHON), Myoclonic Epilepsy and Ragged-Red Fiber disease (MERRF) Leigh s Syndrome dystonia... 

There are several FKBP genes reported to have a defective function in inherited diseases, such as the Williams Beuren syndrome (Williams syndrome) and Leber s congenital amaurosis for FKBP36 (FKBP6) and FKBP44 (AIPL1) mutations, respectively [97-99],... 

Like the mitochondria themselves, some genetic diseases of energy metabolism are maternally inherited. One such disease, Leber s hereditary optic neuropathy (LHON), causes blindness and heart problems. People with LHON have a reduced ability to make ATP. As a result, sensitive tissues that demand a great deal of energy eventually die. LHON sufferers eventually lose their sight because the optic nerve dies from lack of energy. 

Whether distnrbances in CN generation or metabolism can canse disease is controversial, althongh CN imbalance is implicated in Leber s optic atrophy and amyotrophic lateral sclerosis. Important work remains to be done to determine the role of endogenons CN in physiological systems and in disease states. 

Drexler HG, Gignac SM, HofFbrand AV, Leber BF, Norton J, Lok MS, Minowada J. Characterization of Hodgkin s disease derived cell line HDLM-2. Recent Res Cancer Res. 1989 117 75-82. 

Several diseases are caused by oxygen damage from the patient s own mitochondria, which are hot spots for ROS generation. In one of these diseases, Leber s hereditary optic neuropathy (LHON), the mitochondrial proteins that carry electrons and pump protons are broken. The first cells to die are the energy-burning optic nerve cells. The cells die because their broken mitochondria leak too many ROS. 

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