#apaperaday: Duchenne Muscular Dystrophy in Kazakhstan: A Journey from Diagnosis to the Treatment, the Biases and Achievements
In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Duchenne Muscular Dystrophy in Kazakhstan: A Journey from Diagnosis to the Treatment, the Biases and Achievements
Today’s pick is from Journal of Neuromuscular Disease by Jaxybayeva et al on Duchenne diagnosis and management in Kazakstan. A very nice self reflecting paper where authors try to learn and do better. Doi: 10.3233/JND-221559
Authors explain that Duchenne is one of the more common rare diseases and that now mutation specific treatments are available after ataluren approval by EMA and exon skipping therapy approvals by FDA. All approved treatments are available also in Kazakhstan except viltolarsen.
However, they notice there is diagnostic delay in Kazakhstan & underdiagnosis. They calculate 580 Duchenne patients should exist in Kazakhstan based on the 1 in 3500 prevalence. Given that this is more likely 1 in 5000 I think 400 is more accurate. Still, their registry has 84. Average age of a genetic diagnosis was 7.5 years, varying from 4.5 to 17 years. 60 patients in the registry are ambulant, 20 are non ambulant, for 4 it is unknown. 56% had deletions, 2% duplications and 40% small mutations – mostly nonsense mutations (30% of total!).
Authors have an extensive self reflection discussion. The path for genetic diagnosis is gene analysis done after high CK is found when patients present with symptoms. They outline EMGs are routinely part of diagnostic analysis, even though they are not described in care standards.
Gene analysis starts with MLPA to find deletions and duplications, small mutation analysis is done in Germany. Authors stress that there are very little rare disease specialists working in Kazakhstan and clinicians ‘started to give patients more or less proper care’. Steroids are prescribed but often late as there is a stigma on their use and side effects. A reference center is now being established in Astana. Currently clinicians start discussing mutation specific treatments at age 10 – too late. Earlier treatment –> more effective.
Authors outline that they need to make an effort to start steroids earlier as well, as they see the average age of loss of ambulation in Kazakhstan for Duchenne is earlier than other countries. They also want to improve age of genetic diagnosis.
They explain for some patients there was a delay in diagnosis as they were thought to have hepatitis. This happens more often: transaminases are seen as liver damage markers. However, they are also abundant in muscle so plasma levels are elevated with muscle damage.
Authors highlight that they have a surprisingly high number of nonsense mutations. They explain that perhaps this is because there is nonsense mutation specific treatment available, so this mutation type is more actively sought for. They make clear a lot of work has still to be done and that it is not only clinicians in Kazakhstan struggling with this but also in other countries in e.g. the Middle East (featured in earlier #apaperaday). I appreciate the willingness and self reflecting attitude.
This topic was also discussed at the PPMD USA summit meeting. What is needed to help establish expert centers and improve multidisciplinary care is education, e.g. through masterclasses. TREAT-NMD has been given these for DMD, SMA, LGMD and CMD but mostly in Europe, the USA and South America. Educational efforts that are more global and more inclusive are needed – as was also discussed at the TREAT-NMD conference in Vancouver.
I commend the authors for providing this paper outlining not only the current state of things in Kazakhstan, but also how they want to do better and what the problems and challenges are and the consequences of this (i.e. why they have to do better).