Complex 1 Deficiency

A possible cure to complex 1 deficiency or any other mitochondrial disease is quite simple, yet extremely hard to achieve, and that is through gene testing. Gene testing has been happening since 1950′s and there is still no viable way to alter an organisms DNA with no side effects. Genetic modification has always been a conversation concerning moral judgement and ethics, most people believed that gene testing was wrong, altering someones natural DNA can have very severe ramifications if something wrong were to happen, however most scientists believe it would open doors to new revolutionary breakthroughs and change the game of medicine forever. Due to the large number of patients believing that genetic modification is immoral and unethical, most have resorted to treatments that would ease the symptoms instead of be a subject of a experiment. These treatments include a ketogenic diet and consuming supplements to increase the rate of metabolism such as riboflavin, thiamine and biotin etc. A person suffering from this disease would still have to be restricted from exerting too much energy especially during physical activities, activities that involve a lot of movement such as soccer, basketball and hockey are not advised as your body won’t be able to recover from using up that much energy, these treatments would merely keep the patient alive and walking. Moreover the patient would need to take extra care of themselves and follow a strict diet, eat foods that are high in energy, on top of that they would also have a difficult social life, having low energy in the body results in extreme fatigue and often depression, which comes in the way of social interactions and can be terrible to experience each and every day.

Complex 1 deficiency in a nutshell is basically a disease affecting the mitochondria, primarily caused by genetic defects and passed down to offsprings. The DNA that affects mitochondria, which is usuallt referred to as Mitochondrial DNA (or mtDNA for short) is located in the x chromosome of the sex chromosomes. This genetic defect causes a lack of complex 1 in the cristae of the mitochondria, since the whole chain of complexes is required to produce the maximum amount of ATP (energy for cells) that a mitochondria can produce, a lack of complex 1 heavily restricts the production of ATP, because complex 1 actually prevents the other complexes (complex 2, 3, and 4) from producing ATP efficiently. This ultimately means that the body is not receiving the energy it requires, this results in extreme fatigue and low muscle tone, it could become fatal, depending on what organ of the body is lacking complex 1, it mostly occurs in the brain, so in majority of the cases it has been terminal. Some symptoms include episodes of nauseousness and heavy breathing, low muscle tone, extreme fatigue, even depression. 

Parkinson’s disease is a well known disease, the greatest boxer in history Muhammad Ali has suffered from it and it cost him his boxing career and created complications that resulted in his death, but what most people don’t know is that Parkinson’s disease is caused by complex 1 deficiency in the Substantia Nigra which is a region in the brain responsible for movement in the body. Parkinson’s disease causes the sufferer to move uncontrollably, it is a nervous disorder and starts off as slight tremors and shaking, it slowly progresses into full body movement, it can be fatal and very painful, sufferers have trouble sleeping and there muscles cannot handle constantly being moved like that, daily activities become almost impossible at the late stages, this disease can also cause dementia, as it is basically the degeneration of braincells. Just like all other organs, the brain also requires energy, when the cells cannot provide it it causes complications that could be fatal. Most cases of Parkinson’s disease is caused by complex 1 deficiency in the Substantia Nigra, since not enough energy is produced, this region of the brain does not get enough energy, so there is no control over the movements of the body, causing spontaneous contractions of muscles around the body. This is the most recurring case of complex 1 deficiency, however it can happen in other parts of the body, and has a similar affect as in the brain, the organ who’s cells don’t produce enough energy due to the lack of complex 1 in the mitochondria, fail to function, and whether that organ is vital or not determines whether the disease could be fatal. In the case of it being in the brain, it is fatal as the brain is the most quintessential part of the body.

The North American Mitochondrial Disease Consortium is a group of scientists, doctors, nurses, and researchers who have made it their mission to research and eradicated not only complex 1 deficiency, but also every other mitochondrial disease as well. They will do this in 6 steps, firstly there goal is to educate practitioners and the general public about this disease, and raise awareness, then they will make centers of excellence, to provide correct diagnosis and teach practitioners proper technique and practices in terms of diagnosis and treatment for this disease. It will then provide patient support group for families who are suffering with this disease, this support group will be known as United Mitochondrial Disease Foundation (UMDF). It will then foster clinical research to find the natural history of this disease, more basic researches will then be made to dig deeper into these diseases to find other variations of these diseases as well. The final step will be to start very meticulous and innovative clinical trials to find a possible cure or better treatments. Organizations like these are very important as they are giving this disease more awareness and are taking a stand to eradicate mitochondrial diseases altogether.

Above is a chart with data compiled by the 1000 Genomes Project, which is an international project to research and create the most detailed catalogue of human genetic variation. In the chart it is clear that the highest rate of mitochondrial disease exist within the South Asian race, predominantly in Souther Asian countries such as Pakistan, India, Nepal and even some countries in the middle east. The reason behind these countries having these diseases is purely luck, there are no lifestyle habits that lead to this disease, and even modern medicine does not have a cure, someone from that population got unlucky and had mutated genes, and passed them on to offsprings which in return created new generations of offsprings with the disease, ultimately spreading it. The second highest population with this disease are European countries such as Poland, United Kingdom, and Netherlands.

The above image statistics from a data collected by the Royal College of Pediatrics and Child Health, it shows the number of new borns suffering from different mitochondrial diseases globally. It is evident that disorders in Complex 1 are more prevalent than the other mitochondrial diseases, 1 in 8500 new borns around the world suffer from mitochondrial diseases, this means out of the 350,000 infants born per day, 41 could suffer from this disease, 41 infants each day can add up to quite a lot, and these numbers are only rising, with complex 1 deficiency being the most common case of mitochondrial diseases. This is a matter of importance and should be resolved, the people suffering from this disease did not deserve it. The first recorded diagnosis of complex 1 deficiency was in 1988, it was found in the mitochondrial DNA, although mitochondrial DNA were discovered long before then, complex 1 deficiency was relatively recently discovered, and is not talked about quite often, over the years there is a rising rate of patients reporting this disease, and it is caused by the genes spreading around the gene pool of that area. This disease may be quite rare, however it is real, and anybody could be at risk, it is caused by a simple random mutation in the DNA. This disease needs to be talked about more and more research should be done on it, as well as more resources should be spent on finding a cure because it is a real disease and has ruined lives and broken spirits, and is on the rise.

There is no cure or for this disease, as well as no prevention, as this disease is caused by a mutation in the DNA, and is passed down in offsprings, it is an autosomal recessive x-linked trait, meaning it is found in the x chromosome. This would mean that males are at a high risk, as they have one x and one y chromosome as their sex chromosomes, whereas females have two x chromosomes, females would need two of these genes whereas males would only need one to acquire this trait. This disease can only be passed down to offsprings if the mother suffer from this disease, as mitochondrial DNA is only passed down by mothers from the egg cell, this is known as maternal inheritance. Treatments are available but do not guarantee prevention of symptoms, treatments for this disease are usually metabolic therapies such as a ketogenic diet, consumption of riboflavin, thiamine, biotin, co-enzyme Q10 and carnitine.

The above picture shows a baby with hypotonia, this is one symptom of Complex I deficiency, hypotonia can be tested on babies by simply picking them up, if the babies the floppy and are not reacting to being picked up, they are suffering from hypotonia. Other symptoms of complex I deficiency include Myalgia (Muscle pain), exercise intolerance and extreme fatigue. Individuals with complex I deficiency have lactic acidosis, which means their blood has high levels of lactic acid (an acid produced during fermentation in our body, it makes us sore after exercising). This causes rapid breathing, repetitive vomiting, nausea and weakness

This is a visual of the electron transport chain as well as the ATP synthase (Complex V) which is responsible for chemiosmosis. Complex 1 is responsible for removing hydrogen from NADH (a molecule created in earlier steps of cellular respiration) and taking two electrons, these two electrons allow hydrogen to pass through the inner membrane, once all the hydrogen ions collect in the intermembrane space, they undergo osmosis and pass through the ATP Synthase (Complex V) which ultimately generates ATP, which is a molecule that stores energy, it is used by cells as energy.