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Neuromuscular Disorders: Justifying The Relevance of Neuromuscular Diseases In Low Middle Income Countries

Challenges care pathways for neuromuscular disorders in Africa
Jo Wilmshurst

Paediatric neuromuscular diseases are under-recognised and under-diagnosed in Africa, especially those of genetic origin. Factors such as socioeconomic barriers, high burden of communicable and non-communicable diseases, resource constraints, lack of expertise in specialised fields and paucity of genetic testing facilities and biobanks in the African population, making access to and interpretation of results more challenging. The treatment gap between Africa and other HIC’s widen, it is even more important to confirm a genetic diagnosis for affected children to be eligible for drug trials and potential treatments.
There is a massive disparity between LMICs and HICs in the identification and treatment of children with neuromuscular diseases. Africa lacks local genetic biobanks and as such, in the small percentage that are able to access genetic testing, accuracy of these results is debatable. However, for the majority, identification of muscle disorders and accessing specialist care is still challenging. This session will address what we know about NMD in our setting, what we can do with limited resources and how we can make the process more streamlined.

 

Implementation – standard and optimal management, what is the evidence (Cochrane review)
Heinz Jungbluth

The skeletal muscle ryanodine receptor (RyR1) is the main sarcoplasmic reticulum calcium release channel and plays a crucial role in excitation–contraction coupling (ECC), the process whereby a neuronal electrical impulse is translated into intracellular calcium release and, ultimately, muscle contraction. Dominant and recessive RYR1 gene mutations are associated with a wide range of inherited myopathies, including Central Core Disease (CCD), Multi-minicore Disease (MmD), Centronuclear Myopathy (CNM), Congenital Fibre Type Disproportion (CFTD), late-onset axial myopathy, recurrent exertional rhabdomyolysis, and atypical periodic paralysis.
What supporting evidence do we have for interventions that targets patients who have mutations in RYR1 gene? In addition to treatment interventions, what outcome measures are used in this group of conditions. Currently, no cure exists for RYR1-related disorders and no specific guidelines on how to treat people with RYR1-related recurrent rhabdomyolysis. There is no international standard of care in terms of drug treatment prescription and standardised guidelines for the management and treatment of RYR1-related myopathies have not been developed. The tools used to measure outcomes are also not consistent limiting comparison across studies.

 

Novel and innovative screening tools viable and effective as point of entry aids
Carsten Bonneman

Novel and innovative screening tools to identify neuromuscular conditions in resource limited settings. Recognition of specific biomarkers associated with a disorder can allow for targeted genetic testing, thus expediting the diagnostic process. In NMD affecting skeletal muscle, specific patterns of muscle involvement seen using different imaging techniques such as Magnetic Resonance Imaging (MRI) and US have been associated with specific genotypes. Furthermore, machine learning analysis of numeric data generated from neuromuscular imaging has been shown to have a high diagnostic accuracy. Recognition of such gene specific muscle imaging patterns on muscle USS in LMIC allows for stratification of referrals, and may provide evidence of a provisional diagnosis where genetic testing is inaccessible. This would allow for earlier screening of associated co-morbidities and initiation of preventative therapies or interventions. Such diagnostic biomarkers may allow for targeted single gene testing, increasing diagnostic yields and speed of diagnosis. This may contribute to reducing the cost and invasiveness of the diagnostic pathway, by limiting the recourse to other investigations.

 

How the ICGNMD aims to unravel the mysteries of NMDs in Africa
Sharika Raga

How the ICGNMD aims to unravel the mysteries of NMDs in Africa: The International Centre for Genomic Medicine in Neuromuscular Disease (ICGNMD) was launched in 2019. Four SA academic centres are participating in this endeavour with recognition of an expanding network approach to address these core challenges of studying NMD in Southern African populations, and to contribute to the ICGNMD’s ultimate aims of growing international knowledge of the global genetic architecture of inherited NMDs, to enable improved diagnostic and therapeutic outcomes for patients. 
Once common genetic variants in our population have been identified, local testing for the particular variants may be set up, however, this is not without its own challenges. Capacity of laboratory staff, bioinformaticians, genetic counsellors and sustainability thereof is crucial. Specialist/sub-specialists should be able to deeply phenotype patients and correlate this with the genetic variant, however, this is not always a straightforward process and often requires multidisciplinary input.