Issue 24 Understanding Science

The Orphanage

🕒 6 min

Every year, an estimated 1 billion people worldwide are infected by seasonal influenza. In 1980 there were 50 000 reported cases of polio. One of the most infectious diseases of all time was mumps – up to 726 cases per population of 100 000 yearly have been detected around the globe. Unlike such highly contagious diseases, throughout history humankind has faced much rarer diseases, ones we don’t hear much about.

For a disease to be rare in the USA, it has to affect less than 200 000 people. However, the same disease might not be classified as rare somewhere else, since every country sets its own parameters for rare diseases. That’s why a simple Google search for “world’s rarest disease” will give you 10 different results already on the first page. Rare diseases are interesting because it usually takes long to designate them, even longer to detect enough cases to study their characteristics and potential drug targets and the longest to cure them. They even have a special name – orphan diseases, cured by orphan drugs.

The sad side of the story about orphan diseases is that developing any kind of drug to treat them costs the same as developing a drug for a disease that affects tens of thousands of people, but the profit of selling that medicine just doesn’t cover for it. That’s why research and development of orphan drugs is often sponsored by government incentives or by private sector.

Since the term “rare disease” seems to be different from country to country, instead of talking about the rearrest disease, today we are going to talk about the 3 (subjectively) most interesting rare diseases.

The Stoneman syndrome

You can already guess the state of a person with fully developed Stoneman syndrome by reading that name. Officially known as Fibrodysplasia ossificans progressive (FOP), this syndrome causes all connective tissues to turn into bone. Gradually, every tendon, muscle, and ligament in the body of the affected person becomes stiff and non-elastic. It usually starts as restricted body movements in the shoulders and neck, but eventually progresses to legs and ends with complete immobility. The most fascinating thing about this syndrome is that new bony structures are actually part of the second skeleton that grows over the first. What is a benign fall for a healthy person can mean further loss of mobility for those affected, as every injury to the bone stimulates bone growth. Because it affects only one in every 2 million people, this syndrome is not exactly textbook material and is often misdiagnosed as fibrosis or bone cancer. Even though there are no current treatments available, the progression of the disease can be slowed down with personal efforts and careful movements, making sure that minimal damage is done to the bones. The problem is, due to the misdiagnosis, this patients often undergo procedures such as biopsy, which endangers them further. Since in the late stages of the disease eating becomes very painful and restricted, the patients drastically lose weight and often become depressed, which eventually kills them. The only hope for curing this awful state lies in the genetics.

The Alice in Wonderland Syndrome (AIWS)

The next one is less physiological and more psychological. First described in the 1995, AIWS was named after the most pronounced symptom – altered body image, as experienced by Alice in Wonderland. The affected patients report their body parts, usually the head and hands, to be unproportionally bigger than the rest of the body. This symptom is connected with their disordered visual perception, which causes them to see other objects in the wrong sizes and shapes, or in the wrong perspective. For example, the ground may appear closer than it actually is, their car may seem to be too small for them to fit, the hallway may seem very long etc. What’s interesting, this distorted perception is not only limited to the visual sense, but also to the sound they hear (which might appear much louder or too silent), the touch perception (they feel different structures of object under their fingers) and in some cases even distorted taste perception. All of this can be explained on a neurological level – there must be something wrong with the neuron transmission. However, the fact that their perception of time is also distorted, is truly intriguing. Although there is no known treatment for the AIWS, we do know what causes it, or at least we think we do. People who develop AIWS usually suffer from migraines, temporal lobe epilepsy, brain tumors, Epstein-barr-virus infection, while some of them report the symptoms after initiating some psychoactive drugs. Therefore, efforts to treat the AIWS are usually directed to curing the underlying disease. One such case has been described in much detail in the book called “The Man who mistook his wife for a hat”, which we’ve already talked about on this blog.

The Black urine syndrome

Scientifically know as Alkaptonuria, a rare genetically inherited disorder that affects one in one million people globally. Although it can take years for the disease to develop fully, first symptoms can already be detected in toddler years, as dark-stained nappies. If the parents overlook this warning symptom, the disorder will continue progressing and no symptoms are usually detected until the age of 20 or 30. So what exactly causes this dark urine? Because of the inherited genetic mutation, the enzyme which enables our body to break down two amino acids (tyrosine and phenylalanine) is not produced, causing the build-up of a homogentisic acid (a product of tyrosine and phenylalanine catabolism) in the body. Since kidneys are a main way out for the protein building blocks, homogentisic acid is eliminated through urine and as soon as it leaves the body, the oxygen causes its oxidation, which paints the urine in black. However, since this build-up of the homogentisic acid happens throughout the years, a big part of it accumulates in other organ tissues – in every other tissue you can name. For that reason, over the years patients experience other symptoms such as joint and bone pain, brown or grey spotting of the eyes and ear cartilage, discolored sweat, brown coloration of the nails, breathing difficulties, heart congestion, bladder stones, kidney stones and even prostate stones, high blood pressure, skin coloration of the cheeks, forehead, armpits and genital area. Unlike the other two disorders we described here, alkaptonuria has a potential curenitisinone, a “off-label” medicine used to treat patients in the National Alkaptonuria Centre in Liverpool. Although it’s still not an officially licensed treatment, latest studies show a great promise. For those whose parents paid attention when they were still in diapers, there is a possibility to slow the progression of the disease by restricting protein intake with food.

What can I do, except say “WOW”?

Humans often tend to think that something is unlikely to happen to them – until it does. Rare diseases are not so rare when you count them all, and those suffering from them deserve the same treatment options and quality of life like every other person. That’s why raising awareness about orphaned conditions reduces the risk of dangerous misdiagnosis and increases the chance of finding a cure, and that should be important – to every single one of us.

By Đesika Kolarić

Đesika is a pharmacist with an exceptional love for science. Apart from clinical pharmacy, her biggest love is computational biology, which she's currently pursuing through a predoctoral training at Medical university Graz. She loves long walks accompanied by her dog and a good beer.

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