This month, Undiagnosed Children’s Awareness Day aims to raise awareness and increase understanding of the impact and prevalence of undiagnosed or rare genetic conditions. We speak with Dr Jim McGill, a leading expert in laboratory diagnosis and clinical management of a range of metabolic conditions. He has a long history of providing excellent clinical care and compassion to Australians living with a rare disease.

“In Australia, a disease is considered rare if it affects less than five in 10,000 people, which is the same as in Europe. Currently, there are around two million people living with a rare disorder in Australia and around 300,000 in New Zealand. Collectively, rare diseases are more common than diabetes, however they have been neglected by health providers, policy makers and research grants until recently.

“An undiagnosed disorder refers to a medical condition that doctors have so far been unable to identify, therefore it is often the case that the underlying disease is rare. Around 80% of rare or undiagnosed conditions are genetic and are more prominent in children than in adults. One of the main reasons we have undiagnosed disorders is because we haven’t yet recognised all the genetic conditions that exist. This is an area that is continuing to grow as we learn more and more about new genes and gene changes,” said Dr McGill.

Overall, there are more than 7,000 rare disorders currently recognised that are considered to be life threatening or chronically debilitating. Diagnosis can often take time because these conditions are complex, and doctors do not see them often.

“Genetic technology has made a huge difference over the past 5-10 years and we are currently experiencing a period of rapid growth. Two things have happened. Firstly, the ability to test genes and identify the changes that cause disease has improved but more importantly, the price has come down. To give you an idea of how fast this is happening, if you were to re-examine material from a genetic test which proved to be inconclusive a couple of years ago, the chance of being able to get a diagnosis now would have increased between 5-10%.

“We are also getting better at international collaboration. Researchers from all over the world are now feeding information regarding new changes in genes or possible new genes into mega databases. This means that if someone finds what looks like a possible new gene, they can identify that a doctor, for example in Europe or in the US, also has a child that may have a change in that gene. It is then possible for them to exchange clinical information and talk to each other to work out if the children have the same disorder. That’s how new genetic disorders are diagnosed,” Dr McGill.

Rare diseases are complex and often need special treatments. People living with a rare disease, regardless of which specific disease they have, face significant challenges including diagnostic delays, lack of available treatments and difficulty in finding the appropriate health services.

“Only a very small percentage of rare diseases have treatments. This is partly due to the difficulties faced in running a trial. For example, a trial for high blood pressure could easily attract over 1,000 people from say Brisbane. However, a trial for a condition such as N-acetylglutamate synthetase (NAGS) deficiency, where there is only one case in Australia, would be lucky to have 20 people from all over the world. Unfortunately, it is also likely the trial would take place in the US or Europe so people from Australia would either have to move or wait until the study enlarges enough to involve Australian families – that’s if there even is a treatment.

“From a drug company perspective, if you’re treating blood pressure, you may have 10,0000 people using your drug in Australia. However, if you are treating rare disorders, you may only have five patients across the whole of Australia. The mark-up to make it worthwhile for companies to develop these treatments is therefore much greater and tend to be very expensive for patients,” said Dr McGill.

In 2020, the Minister for Health launched the National Strategic Action Plan for Rare Diseases, the first nationally coordinated effort to address rare diseases in Australia. The Action Plan has been a positive step forward and aims to increase awareness and promote earlier, more accurate diagnosis and treatment for those living with rare diseases by being person-centred, through equity of access, and sustainable systems and workforces.