A recent study published in the Journal of the American Heart Association has demonstrated that high cardiac biomarkers, coupled with low BMI and a poor respiratory profile are important risk factors that could put Duchenne muscular dystrophy patients at risk of premature death.
Duchenne muscular dystrophy, also known as progressive muscular dystrophy, is a hereditary disease with a recessive inheritance factor linked to the X chromosome, which means that it manifests mostly on male patients, and only very rarely in the opposite gender, who are mostly carriers and transmitters of the disease, without actually experiencing its symptoms. Among all the muscular dystrophies, Duchenne is the most common variation. It is a myopathy of genetic origin that prompts the destruction of the striated muscle cells, replacing them with adipose tissue. The disease itself is created by abnormalities in the gene responsible for processing the dystrophin protein, which is charged with connecting the actin filaments to the extracellular matrix. Through this mutation, the striated muscle cells begin an accelerated process of degeneration as they are not able to connect to the extracellular matrix to receive sustenance.
Like many other types of muscular dystrophy, Duchenne usually has its beginning during the patient’s infancy and is characterized by progressive muscular atrophy with a proximal origin. In other words, the disease affects the structures closest to the core first and spreads to the rest of the body as time passes. As a result, the person may experience signs and symptoms such as loss of reflexes and a noticeable gain in muscle mass (hypertrophy). These diseases are, by nature, progressive, and will evolve to the point of imposing serious limitations or premature death on the patient.
Despite being the most common variation of the disease, Duchenne muscular dystrophy presents a grave clinical picture and has its origins much earlier than other types of dystrophies, such as Becker’s. With a rapid advance in muscle degeneration that generates complications in the person’s mobility, muscle spasms, scoliosis, and pseudo-hypertrophy (caused by the replacement of striated muscle tissue for adipose tissue), those who suffer from this condition rapidly deteriorate and usually meet an early death near their twenties due to cardiac or pulmonary arrest.
Generally speaking, muscular dystrophy can be distinguished from similar neuromuscular disorders due to their hereditary factor and clinical pictures. However, there are 4 key elements of any given muscular dystrophy that makes them stand out among similar conditions:
- They are a primary myopathy, characterized by muscle degeneration of internal origin
- They have a genetic origin
- They are progressive
- At some point of the disease, the muscle tissue degenerates and dies
The study conducted in 2017 discovered that there may exist several elements that, when present in Duchenne patients, are important indicators that could lead to their premature death.
The study observed 43 male Duchenne patients using their medical, laboratory, and demographic information, which was pulled from their respective medical records. The profiles of those who had survived and were still living were determined and contrasted with the patients who had expired due to the disease. Through this relation, researchers discovered that those who had died had less body weight and a lower body-mass index than the survivors upon the time of their deaths. Those who died weighed, on average, 48.3kg, while those who survived weighed 69.4kg. Furthermore, the survivors showed an average BMI of 25.8 kg/sqm, while the dead had an average of 17.33 kg/sqm at the time of their deaths. Lastly, the group of patients that died had significantly more underweight subjects than those who survived (75% vs 11%).
Weight, however, was not the only risk factor discovered, as the patients that expired showed a noticeable weakening of their respiratory muscles in the form of reduced maximal inspiratory pressure, when compared to the survivors. The results showed that those who survived had more than double MIP than their counterparts (33 vs 13 cmH₂O). Alongside said weakening of respiratory muscles were the systolic blood pressure and N-terminal pro-brain natriuretic peptide levels, which were noticeably different in those who survived in relation to the expirees.
While this study had little purpose in finding a cure or a way to prevent Duchenne, it offered a reliable source of information to gauge the risk and extent of the patient’s disease.
Genetic origin of Duchenne muscular dystrophy
What makes Duchenne muscular dystrophy such an aggressive disease when compared to, say, Becker muscular dystrophy revolves around the nature of the mutation that causes it. The mutations that provoke Duchenne have as consequence an altered ARNm transcription, which results in the creation of proteins with a different chain of amino acids than expected, resulting in the appearance of premature stop codons and a dysfunctional protein that rapidly degenerates. Consequently, the patients who suffer from Duchenne completely lack the capacity to produce dystrophin, causing a very rapid and aggressive degeneration of muscle tissue.
Upon closer study of the dystrophin genes in Duchenne patients, it was observed that those who suffer from the condition might have one or many mutations in one or several exons of said genes. Specifically, around 60% to 70% of cases show deletions, 10% of cases show duplicates, and the remaining 20% to 30% show small writing errors on the gene. Luckily, those who suffer from Duchenne as a result of gene deletions can be subjected to gene therapy, which would allow them to produce functional dystrophin, effectively preventing the symptoms from surfacing. However, these treatments are expensive, as well as widely unavailable to the general public.
As of 2016, the treatment for Duchenne revolves around measures to support the patient’s condition. Physiotherapy, psychomotricity sessions, logopedia, occupational therapy, and the close monitoring and control of symptoms are measures dedicated to improving the functionality and quality of life of Duchenne patients. By evaluating which symptoms the patient possesses, and which have still yet to develop, the clinician may plan an appropriate treatment plan for the patient.