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#apaperaday: Time to diagnosis of Duchenne muscular dystrophy in Austria and Germany

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Time to diagnosis of Duchenne muscular dystrophy in Austria and Germany

A paper from Science Reports by Hiebeler et al on the time to diagnosis of Duchenne in Austria and Germany – and also other comparisons between the patients in these countries. DOI: 10.1038/s41598-022-27289-2

Authors explain symptoms in Duchenne patients generally become apparent at age 3 years, but that speech delay and high creatine kinase (CK) in blood can lead to diagnosing the disease presymptomatically. I would argue that these signs are also symptoms…so post symptomatically. You can argue that these are semantics, but it is important for people to understand that Duchenne does not ‘start’ at ~3 years of age. It starts earlier – patients have high CK even at birth and significant amounts of muscle are lost already when symptoms start.

Back to the paper: authors have a German registry with 766 patients. In principle the registry is also open to Austrian patients (same language), but this is not much used. Authors therefore actively reached out to Austrian patients with a questionnaire.

57 patients out of an expected 200 replied. These were aged 4-34 years and 93% were living with their parents. Symptoms became apparent between 9 months and 7 years, on average at age 3 years. Most common: problems climbing stairs, rising from floor and late ambulation. Speech delay and a waddling gait were also reported. 40% of patients were accidentally diagnosed because high CK was noticed in an unrelated check. In 50% of patients, diagnosis was made 6 months after symptoms were apparent. In 18% however it took over 2 years.

A genetic diagnosis was confirmed in only 86% of cases. For older patients often this was based on a biopsy and dystrophin staining. 52% used steroids: 78% of the 6-18 year olds, while 11% of the >19 year olds used them (58% had used them in the past).

Loss of ambulation was at a mean age of 10.3 years. Psychotherapy was provided to only 29%. 94% of patients received all care from their family. Now to the comparison with Germany: from the 766 patients (age 0-45 year) data was not available for each of the items asked in Austria.

Also in Germany symptoms appeared at age 3 years, with a diagnosis happening at 3.5 months later. A genetic diagnosis was only done in 80% (again less in older patients). 47% were on steroids, 63% for aged 6-18 yrs.

Interestingly, 14% of patients under 5 yrs were on steroids in Germany, vs 60% in Austria. Age at loss of ambulation was 11.5 yrs for German patients. Authors discuss that a timely diagnosis for Duchenne is important but challenging.

They indicate looking at different countries and learning from what works and where things go wrong can teach everyone globally to improve. Delays between first symptoms and diagnosis vary between countries: Germany 4.7 mo, Italy 10 mo, Austria 11.5 mo, UK 19.2 mo, USA 26.5 mo.

The delays in the UK and especially in the USA are due to different setups where health care providers are less familiar with the disease and where in the USA there are geographic hurdles (distance to expert sites) and insurance problems (genetic test not reimbursed).

Authors indicate that an earlier diagnosis is important due to access to counseling and mutation specific treatments. They say that one should not only focus on reducing the delay between symptoms and diagnosis, but also improve recognizing early signs.

For a nice paper on early signs I refer to this one: https://pubmed.ncbi.nlm.nih.gov/32692451/ Duchenne Parent Project Netherlands and TNO Nieuws collaboration. Another thing authors stress is that in patients with cognitive problems (1/3) diagnostic delays can happen because motor problems are missed.

I think we can all learn from the very short time between showing symptoms and diagnosis in Germany but also appreciate that authors try to improve more and outline that even though these are averages, there are also cases where it takes longer.