Progeria is one of the rarest diseases in the world, as it only affects about 1 in 4 million children. It is caused by one, single, tiny mutation within the gene code that changes a nucleotide base from cytosine to thymine. This causes an abnormal protein called progerin to be created. This protein acts as an imposter and tries to take the place of a normal protein by going into the nucleus of the cell and sticking into places where normal proteins should go. The only problem is that the progerin is toxic and misshapen, and it begins to destroy the structure of the tissue created. This leads to many problems in development, and ultimately, results in the main symptoms of progeria.
https://vimeo.com/75526698
https://vimeo.com/75526698
Whom does this disease affect?
The disorder is considered autosomal dominant, which means if any form of the progeria gene is present, it will be inherited. One copy of the mutated gene is sufficient to cause the disorder. Usually, people with Progeria do not reproduce, so the disease is not passed down. The mutation is found on chromosome 1, and therefore is not sex-linked. It is dependent on new mutations in the LMNA gene, so is random. Surprisingly, the mutations almost always occur in people with no history of Progeria in their family. Inheritance of the disease and likelihood of contracting the disease is not dependent on race or gender.
What is the biology behind the disease?
The LMNA gene in cells is very important to the overall structure of the cell, and ultimately the organism. It produces a protein called Lamin A, which is a structural scaffolding that holds the nucleus of a cell together. When progeria is present in an organism, the Lamin A protein is mutated into progerin. The process of mutation is because one nucleotide base on the gene is changed from cytosine to thymine. This progerin is missing about 50 amino acids near the end of its sequence. The progerin makes the nucleus unstable. This leads to premature aging and disease. As the progerin (misshapen protein) is constantly fitted together, the structure created is unstable and contorted. This mutation is found on chromosome 1, and has some very serious and drastic symptoms associated with it.
what are the symptoms?
Because the mutation that causes Progeria affects the proteins in the body, many visible changes and symptoms occur in the patients. There is a lot of cellular instability in the body of someone diagnosed with Progeria, and this leads to premature aging. Infants with the disease are born looking healthy, but begin to display many characteristics of accelerated aging at around 18-24 months of age. The symptoms include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, and cardiovascular disease and stroke. Outwardly visible signs include a narrowed face, small lower jaw, thin lips, and a beaked nose. The head is disproportionately large compared to the face, and patients have 'prominent' eyes, with an incomplete closure of the eyelids. Hair loss, wrinkled skin, visible veins, a high pitched voice, and loss of fat are also common. In more severe cases, fragile bones, hearing loss, and abnormal tooth formation may occur. On top of this long list of symptoms, Progeria causes severe progressive heart and blood vessel disease. This is the main cause of death, and the average life expectancy for those with Progeria is 13 years. Some with the disease may live up to 20 years.
Is there a cure?
It was previously believed that no cure could ever be developed for Progeria. This isn't entirely true, because although there is no solid cure, there is something that comes close. Lonafarnib is a drug that was originally developed to treat cancer, but has been proven effective for treating progeria. Every young child that has received the treatment has improved in one or more of four ways: gaining additional weight, achieving better hearing, experiencing improved bone structure, and having increased flexibility of blood vessels. Twenty-eight children from six different countries were all tested with the drug, and they all produced significant results. The most prominent benefit was the weight gain, which is important because children with Progeria have severe failure to thrive. Also, more importantly, major blood vessels in patients could have improved flexibility. Accelerated cardiovascular disease is the main cause of death in Progeria, so this drug is a major breakthrough. All of the research was conducted and funded by the Progeria Research Foundation. Unfortunately, this drug is not yet commercially available.