Mitochondrial Diseases: LHON
Mitochondrial Diseases: LHON
The respiratory processes and chains which occur in the mitochondria are essential in the generation of 90% of the energy used in the human body. Mitochondria exist in every cell of the body, apart from the red blood cells, a fact which illustrates how important they are in terms of energy needs in the human body (Gorman et al., 2016). For some reason, there could be failures in the mitochondria which affect their functions. With the collapse of the mitochondria, there is a reduction in the energy which is generated in the cell. What follows next is the injury of such cells, or even the cells may die. Continuous repetition of the process leads to a massive organic and system failure (Gorman et al., 2016). These failures are what will lead to mitochondrial diseases.
Mitochondrial diseases are disorders that arise as a result of the unsatisfactory function or failures in the respiratory chain within the mitochondria (Gorman et al., 2016). Typically, such a chain is the most critical process of aerobic metabolism. The most affected body parts and tissues are those who are solely reliant on this aerobic process. The most commonly affected organs are the muscles, brain, heart, lungs, and nerves, which take up the most significant percentage of the aerobic energy produced in the body. Making up the mitochondria structure are several genetic strands that become dysfunctional units to result in mitochondrial diseases (LHON, 2019). Majorly, it is a result of the mutations of the encoded genes, and the effect of the DNAs, either nuclear or mitochondrial. There are several types of mitochondrial diseases: LHON, Leigh’s Syndrome, Neuropathy, Diabetes mellitus, myopathy, among others. A majority of the mitochondrial diseases affect a single part of the body, while others have combined effects on several body parts. In this paper, Leber’s Hereditary Optic Neuropathy affects the optic nerves leading to failure of central vision.
Leber’s Hereditary Optic Neuropathy, LHON
Genetic Disease Description
Leber’s Hereditary Optic Neuropathy is a genetically transmitted mitochondrial disease that was first diagnosed by a German Doctor, Theodore Leber. The mitochondrial inheritance is passed from the mother to the offspring, and as a result, it affects the axons and the retinal ganglion cells. The mutated mitochondrial genes cannot be moved from the father to the family. Noting that the human’s optic capability is a combined function of the brain, the eyes, and the nerve system, Leber’s Hereditary Optic Neuropathy mainly interferes with the nerve system of the optics. This interference will, therefore, mean that the optic signals are not transmitted between the brain and the eyes once the transmission system is destroyed. The LHON occurs because of the mutation of the genetic materials in the mitochondria. The specific genes which are affected in the modification are MT-ND4, MT-ND6, or else MT-ND1, which are in the mitochondrial DNA (mtDNA) (Carelli et al., 2016). These genes are among the responsible features for the protein metabolism to convert the fats, sugars, and protein into energy. The dysfunction of these nerves is, therefore, responsible for the death of the optic cell nerves.
Signs and Symptoms of LHON
The condition generally starts with a gradual process of diminishing central vision, which is always a painless process. A typical case will begin by losing the fundamental vision ability in one eye, and then after some weeks or months, the same also occurs gradually in the other eye (Majander et al., 2017). With time, all of the eyes go beyond the legal mark of blindness declaration, which is 20/200. With the condition affecting the central vision, there is an onset of blurry or cloudy vision, which becomes severe as the size of the blind spot increases over the months. With time, the affected person loses the inability to recognize faces, read the standard text sizes, and even will not be able to drive. This loss of vision results from the death of cells on the optical nerves responsible for the transmission of information from the brain to the eye.
With time, the condition is expected to worsen; that is, the person can be able to lose their full eyesight gradually, or else they develop peripheral vision. This case of peripheral vision may not be the case in some instances as it leads to permanent loss of vision (Majander et al., 2017). The people with this condition may not externally look like they are blind. Unless they are using a cane or a guide dog to walk, other people may judge them as being rude by the way they may stare at them, or they are judged for not responding to people because they do not see anything. The cases that develop the peripheral vision will, in most cases, be gazing straight in front of them so that other people will not recognize their problem. To see someone, the peripheral vision cases will either seem to look up or sideways to acknowledge anything.
LHON has one primary symptom, which is a gradual loss of vision. There is a. however, a report of another class of the LHON called Leber’s Hereditary Optic Neuropathy Plus (LHONPlus), which has additional symptoms. Apart from the loss of vision, the LHONPlus patient may also have problems with motion, cardiac dysfunctions (electrical signals for the heartbeats). Further, such a condition causes weak body muscles resulting in body tremor, numbness, and incoordination of the body tissues.
LHON Demographics
There no specific research and statics on the prevalence rates of rare conditions. A case study in Finland and England, however, estimates that Leber’s Hereditary Optic Neuropathy affects 1 in about 50 000 people. In the United States, about 100 people lose their central vision due to this condition annually. These people add up to the 4000 cases that are already affected by this condition in America (Majander et al., 2017). In the whole world, an estimate of about 35 000 people are thought to be living with the LHON mutation vision, or they are already blind because of the condition (LHON, 2019).
Additionally, the disease has a higher bias for the male gender than females. The genetic mutation is inherited from the mother to all her children, but then the females will rarely show any sign of the condition. This condition is therefore added to the list of sex-specific genetic inheritance conditions. Out of the whole population who are already affected by Leber’s Hereditary Optic Neuropathy, above 75% of them are males, while females take up to about 25% of the total cases (Carelli et al., 2016).
In terms of age distribution, the condition is rarely noticed in children (Majander et al., 2017). Whereas the start of the loss of central vision can start at any age, there is always a peak age. For the males, the peak age is between 14 to 26 years old. There is no specific record of the peak age for the females (Giordano et al., 2015). The bottom line, however, is that as long a person has the Leber’s Hereditary Optic Neuropathy mutation, they can be affected at any time of their lives.
Causes of LHON
Leber’s Hereditary Optic Neuropathy is primarily a genetic disorder, and there is no other recorded cause. This cause shall, however, focus on what triggers the loss of vision to people with the mutated genes of mitochondria. There a significant number of people who harbor Leber’s Hereditary Optic Neuropathy mutation, yet they still have a full and healthy sight (Carelli et al., 2016). Such people are referred to as carriers, also known as unaffected carriers. The populations who have lost their central vision resulting from the LHON mutation are called the affected.
In a study conducted on the affected and the unaffected carriers, it was noted that some external environmental factors trigger the loss of vision. Among the triggers, the use of tobacco, or worse, a combination of smoking and alcohol is responsible for most cases (Giordano et al., 2015). Another study also showed that patients with ‘tobacco-alcohol-amblyopia’ had a major of the mtDNA mutation, which results in LHON (Carelli et al., 2016). Together with the deficiency of vitamin B12 and folate in the body, there is an increased effect on optic neuropathies, which is the same as LHON.
LHON Diagnosis
With the noticed hereditary pattern, Leber’s Hereditary Optic Neuropathy is easily detected in some families. For a family with a history of the condition in the bloodline of the mother, the offspring should, at any point in their lives, expect the loss of central vision; this will be a painless process (Matthews, 2015). Bearing the mutated gene does not, however, mean that one will lose their sight. A good number of people have the gene but are having healthy eyesight. Of the carriers, only half of the men are at risk of losing central, and a quarter of the females.
For cases where a person does not know the family history in terms of the LHON mutation, a person experiencing sudden painless loss of vision is taken through some tests. The other possible causes of the loss of vision are tested and treated. Possibly, MRI is also conducted to rule out potential damage or growth in the brain, as well as to check in case there is any physical damage of the optic nerve (Matthews, 2015). The retina is also cross-examined. Once all these are ruled out, a genetic test of the rare LHON condition commences after that.
Precise laboratory tests on the saliva and blood are used in determining a possible LHON mutation. Possibly, a GeneDX test is done for a chance of detecting up to 20 mutations of Leber’s Hereditary Optic Neuropathy, which are very rare (Meyerson, Van & McClelland, 2015). Other forms of genetic tests in the laboratory are only able to test for only 3 cases of the mutations. Another possible test to detect the LHON mutation is the comprehensive mitochondrial examinations, which are done in the EGL Genetic laboratories (Meyerson, Van & McClelland, 2015). Once the LHON is detected in the person, it is assumed the whole maternal bloodline is carriers of the condition. Further tests will, therefore, be not necessary for the rest of family members with suspected loss of central vision.
Patient Treatment and Care
Leber’s Hereditary Optic Neuropathy has no treatment which is medically approved by the medical and pharmacy bodies. It is only in Europe where a medication called Raxone was approved by the European Medicine Agency to be used on a patient with LHON (Meyerson, Van & McClelland, 2015). This medication can only be used at an early stage of the gradual loss of central vision.
Where a patient has been diagnosed with Leber’s Hereditary Optic Neuropathy condition, specialists suggest that the family should avoid the earlier mentioned triggers. Both the people who are affected and the ones not affected should avoid all forms of smoke: stoves, tobacco, and chemicals. Additionally, they should also avoid the usage of some medications with microbial and Ringer’s lactate (Carelli et al., 2016). All these are capable of putting more pressure on the already mutated mitochondria, which would, therefore, quickly result in the loss of central vision.
Conclusion
Mitochondrial disorders take time to notice, diagnose, and manage, especially now that they are inherited conditions. For situations like the LHON condition, hereditary patters cannot be controlled for the few people who are already living with the mutated genes. Care should just be taken to avoid the triggers, especially in the males who are the most affected by the disease (Giordano et al., 2015).
Even though Leber’s Hereditary Optic Neuropathy is a rare condition in the world, there is a lot of researches on it (Meyerson, Van & McClelland, 2015). The studies are geared towards finding a medication for the condition as well as mitigation measures to the prevention of loss of vision to the unaffected. For the ones who are already affected, the community of patients living with the mutation and the society for rare diseases is calling upon special care for such patients (LHON, 2019). It is emotionally draining for a person to lose sight in their adulthood gradually. The individuals who suddenly start experiencing blurred vision together with the families are often for some time referred to counselors for psychological help. The public should, therefore, be supportive to help them be able to adapt to the new life which they shall have for the rest of their lives.
References
Carelli, V., d’Adamo, P., Valentino, M. L., La Morgia, C., Ross-Cisneros, F. N., Caporali, L., Maresca, A., Loguercio Polosa, P., Barboni, P., De Negri, A., Sadun, F., Karanjia, R., Salomao, S. R., Berezovsky, A., Chicani, F., Moraes, M., Moraes Filho, M., Belfort, R., Jr, & Sadun, A. A. (2016). Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion. Brain: a journal of neurology, 139(Pt 3), e17. https://doi.org/10.1093/brain/awv339
Giordano, L., Deceglie, S., d’Adamo, P., Valentino, M. L., La Morgia, C., Fracasso, F., … & Parente, D. (2015). Cigarette toxicity triggers Leber’s hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation, and ROS detoxification pathways. Cell death & disease, 6(12), e2021-e2021.
Gorman, G. S., Chinnery, P. F., DiMauro, S., Hirano, M., Koga, Y., McFarland, R., … & Turnbull, D. M. (2016). Mitochondrial diseases. Nature reviews Disease primers, 2(1), 1-22.
LHON. (2019). Leber’s Hereditary Optic Neuropathy. Retrieved from https://www.lhon.org
Majander, A., Bowman, R., Poulton, J., Antcliff, R. J., Reddy, M. A., Michaelides, M., … & Yu-Wai-Man, P. (2017). Childhood-onset Leber hereditary optic neuropathy. British Journal of Ophthalmology, 101(11), 1505-1509.
Matthews, L., Enzinger, C., Fazekas, F., Rovira, A., Ciccarelli, O., Dotti, M. T., … & Lukas, C. (2015). MRI in Leber’s hereditary optic neuropathy: the relationship to multiple sclerosis. J Neurol Neurosurg Psychiatry, 86(5), 537-542.
Meyerson, C., Van Stavern, G., & McClelland, C. (2015). Leber hereditary optic neuropathy: current perspectives. Clinical Ophthalmology (Auckland, NZ), 9, 1165