A Battle Against the Clock
Imagine feeling like you’re constantly living in a different time zone. This is the reality for individuals living with non-24 hour sleep-wake disorder (non-24), a circadian rhythm disorder which occurs when one’s biological clock does not line up with the 24-hour day clock. In humans, the natural body clock is slightly longer than 24 hours, but changes in light stimulate the release of hormones which reset our body clock so that we are adapted to living on a 24-hour clock (Figure 1).1 Non-24 is a rare disease which occurs most commonly in individuals with total blindness because they cannot sense the changes in light that help reset our natural body clock.1 Working a 9-5 job has been accepted as normal in most societies around the world, but what if your body ran on its own cycle that doesn’t match the 9-5 lifestyle?
Non-24 results in varying symptoms in those affected but extreme tiredness during the day and alertness at night, sleep deprivation, and reduced energy are all common symptoms of the disease.2 Often, individuals with non-24 will notice a shifting sleep cycle due to their misalignment with the 24-hour clock. These symptoms can have an impact on the individual’s physical health and also severely affect their social life.2 Non-24 can be a detriment to an individual’s relationships with family and friends, their work and school schedule, and social life.
The symptoms of non-24 alone can be tough to deal with, but it makes it much more difficult when others aren’t sympathetic to the obstacles of living with non-24. In the first place, it is often very difficult to get a diagnosis of non-24 because most physicians lack enough knowledge of the disease and often the symptoms are misattributed to other diseases such as depression. Once a patient receives a proper diagnosis being aware of the disease can make life a little easier but having the proper support from family, friends, and coworkers is also very important. For those who don’t understand the disease or believe in its legitimacy might think the individual is simply lazy and they can make it difficult for the patient especially when it comes to keeping a flexible schedule.
There are a few treatment options available for individuals with non-24, with the three main modes of treatment being phototherapy, medication, and treatment with melatonin.3 Phototherapy is not effective in totally blind individuals with the disease as it is delivered by increasing light exposure a few hours prior to wake-up time in order to reset the body clock. This treatment must occur at the same time every day in order to be effective.3 The drug Hetlioz has recently been approved by the FDA for use in treating non-24; it has been designated as an orphan drug and targets the melatonin receptor which controls the sleep-wake cycle.4 Hetlioz is to be taken every night at the same time just before going to bed. Melatonin is a hormone that helps control the sleep-wake cycle, but it can also be used as a drug that can be taken at the same time each night to adjust the sleep-wake cycle. However, it is less specific in its binding compared to Hetlioz which binds the M2 receptor with a higher affinity which helps control the circadian rhythm.3
Having treatment options available for those suffering from non-24 is exciting because it is a rare disease, although these treatments do come with side effects. Hetlioz is often associated with side effects such as headaches, nightmares, a disturbed night’s sleep, and drowsiness.3 Despite these side effects most patients would rather suffer through them and be able to participate in the normal 9-5 lifestyle. Another problem with these treatments is the high cost associated with them; for example, Hetlioz can cost up to $9,728.60/month in the US.1 Hetlioz is a relatively new drug (approved by the FDA in 2014), and its long-term effects are not known.5 However, it is known that denying the body’s natural circadian rhythm can lead to other diseases such as cancer, diabetes, and heart disease. This can make it difficult for an individual with non-24 to make the decision to treat their disease as it may ultimately shorten their life.
Although non-24 is most common in totally blind individuals, it also occurs in a small percentage of sighted individuals such as Jonathan Hume who was diagnosed with the disease at 22 after suffering from its symptoms for years.5 For Hume, the symptoms started at a young age when he was notably irritable, lethargic, and had trouble sleeping and waking up during middle school. His symptoms escalated when at age 16 he couldn’t wake up for classes, and his grades were greatly affected; non-24 even caused him to sleep through exams.5 When he got to university things were a little easier with optional classes and a more flexible schedule in general, but when he went to a general practitioner with his symptoms he was dismissed and told it was simply from ‘being a student’ and ‘partying too much.’5 It wasn’t until Hume began his Master’s when he went to a specialist in travel medicine, and jet lag in particular. After tracking his sleep times, Hume was correctly diagnosed with non-24 (Figure 2). Since being properly diagnosed, Hume has found being aware of his disease makes it much easier to live his life and plan a schedule around his body clock.
Non-24 is a rare disease which can take a serious toll on a patient’s life in numerous ways, although with proper diagnosis and a treatment plan it is possible to overcome. A disease that affects patient’s life in the way non-24 does requires the help from others to make it possible for them to maintain a social life and hold down a job; by working with them instead of against, a difficult situation can be made a little easier.
1. Daly A. Non-24-Hour Sleep-Wake Disorder: Disease Overview and Treatment Options - See more at: http://stage.uspharmacist.com/article/non-24-hour-sleep-wake-disorder-disease-overview-and-treatment-options#sthash.2A8uJwTj.dpuf. US Pharmacist. 2015;40(6):48-52.
2. Non-24-Hour Sleep-Wake Disorder - NORD (National Organization for Rare Disorders). NORD (National Organization for Rare Disorders). 2017. Available at: https://rarediseases.org/rare-diseases/non-24-hour-sleep-wake-disorder/.
3. Treatment & Care. Sleepfoundationorg. 2017. Available at: https://sleepfoundation.org/non-24/content/treatment-care.
4. FDA Approves Hetlioz: first treatment for non-24 hour sleep-wake disorder. Fdagov. 2017. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm384092.htm.
5. Hume J. Non-24-Hour Sleep-Wake Disorder: When Night And Day Keep Changing. Rare Disease UK. http://www.raredisease.org.uk/news-events/news/non-24-hour-sleep-wake-disorder-when-night-and-day-keep-changing-1/. Published 2016.
Cite This Article:
Smith E., Zheng K., Chan G., Ho J. A Battle Against the Clock. Illustrated by H. Zhang. Rare Disease Review. February 2017. DOI:10.13140/RG.2.2.19072.02564.