The common story
There is a common story among children and families affected by Sanfilippo syndrome: it often starts in the first two years of life, when children experience frequent ear and respiratory infections. They might get grommets and have their adenoids removed. Then parents notice a speech or other developmental delay around two years, which progresses to behavioural and sleep issues when their child is around 3-4 years old. There might be a diagnosis of autism or ADHD, but things still don’t quite add up. Parents go from doctor to doctor to understand what is happening. Eventually, they may receive the devastating diagnosis of Sanfilippo syndrome, which tells them of the next stages of the disease - dementia, with the progressive loss of skills, speech, and thinking abilities, leading to death often before adulthood.
This story will affect one baby in around 70,000 births, but there is something that could change the story for those affected by Sanfilippo: access to an early and accurate diagnosis.
The challenge of early diagnosis
There are many reasons why early diagnosis is challenging for Sanfilippo and the group of related conditions known as mucopolysaccharidoses (MPS),1 as described in a recent article by researchers in Gdansk, Poland. MPS disorders are rare and diverse; even patients with the same type of MPS can show very different symptoms. Often, the early signs of MPS are not specific to these conditions or may only become severe enough to warrant attention over time. MPS diseases also affect multiple body systems, meaning various specialists may look at particular symptoms in isolation and not join the dots to recognise the underlying cause.
Why late diagnosis is a problem
A long diagnostic odyssey causes uncertainty and stress for families. Children may be subjected to multiple tests, medications and other therapies that are invasive, ineffective, and potentially harmful.2 Before a correct diagnosis is received, children with Sanfilippo are typically misdiagnosed with Autism spectrum disorders, ADHD, or another rare disease.1
Misdiagnoses and late diagnoses make it harder for clinicians to treat the neurological symptoms of Sanfilippo in time to make a difference. Results from pre-clinical studies and clinical trials indicate there is likely to be a limited treatment window – the younger the patient, the greater the chance a therapy will halt or slow neurodegeneration.3
The ideal time to treat patients is currently thought to be before two years, but, as the common story above illustrates, very few patients are diagnosed this early. Most are not diagnosed until at least four years of age. For individuals with slower progressing subtypes or attenuated forms,4 a diagnosis is likely to come even later - and some may remain undiagnosed for decades.2
How can we rewrite the story?
Raising awareness and educating primary physicians, other specialists, and allied health professionals on the collection of early signs and symptoms that could raise a red flag for Sanfilippo syndrome or other rare neurodegenerative diseases in children is vitally important.
However, newborn bloodspot screening (NBS) could provide the earliest chance to identify patients. Also known as a heel prick test, this non-invasive test screens babies for many rare yet devastating diseases within the first few days of life.
Many criteria need to be met to add conditions to the list of disorders tested for in Australia’s NBS program, and Sanfilippo is yet to be added. Pilot screening studies that include Sanfilippo types A and B have been run or are underway in Taiwan and New York and will help to make a case for NBS for Sanfilippo in those countries as well as Australia.5,6
These steps to improve early diagnosis would remove the long, distressing diagnostic odyssey for families. It would enable individuals with Sanfilippo to access better clinical care right from the start and access clinical trials of potentially life-changing treatments. It could provide families with choices for future family planning.
By providing an earlier diagnosis for patients and their families, we could rewrite the story for Sanfilippo.