Summary of New Hope for Patients With a Rare Incurable Disease:
Researchers from multiple Swiss research institutions have identified a molecular diagnosis strategy that correctly diagnosed 84% of patients with the rare metabolic disorder methylmalonic aciduria (MMA), which affects one in 90,000 newborns. The team took a multi-omics approach, comprising genomics, transcriptomics, proteomics and metabolomics, to expand significantly the diagnoses beyond DNA sequencing. The diagnostic strategy included examining the RNA transcripts of the patients’ genes and many of their proteins. The new method will help ensure patients receive the correct treatment at an earlier stage, according to the study published in Nature Metabolism.
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Methylmalonic Aciduria — What is it and How Can it Be Managed?
Methylmalonic aciduria (MMA) is a rare genetic disorder affecting approximately one in 90,000 newborns. This metabolic disease comes from both parents carrying the genetic predisposition for it, which causes the patient to have a defective enzyme needed for energy metabolism. The consequence leads to a specific metabolite accumulating in the body, which can cause harm instead of being broken down for energy. Although there is no known cure for MMA, scientists from various Swiss research institutions have identified novel methods to help diagnose and manage patients.
Why is MMA a Cause for Concern?
Patients diagnosed with MMA are affected by both delayed growth and kidney failure, and they may develop severe neurological impairment. Many affected children and adolescents often use wheelchairs and do not survive till adulthood. In addition, MMA is considered incurable; however, scientists from the University Children’s Hospital Zurich and other institutions in Switzerland have found ways to identify the underlying mechanisms of the disease, which can help to develop new approaches for MMA therapies.
How did Researchers Identify, Analyze, and Diagnose MMA?
Researchers initiated and funded the project with the ETH Domain strategic focus area Personalized Health and Related Technologies (PHRT) and examined 210 biopsies in detail from patients worldwide. For the first time, MMA was studied using a multi-omics approach, including genomics, transcriptomics, proteomics, and metabolomics. The molecular analysis was carried out at PHRT’s Swiss Multi-Omics Center (SMOC) in Zurich.
Furthermore, by expanding the molecular investigation, researchers took into account not only the gene’s consequences but also RNA, proteins, and protein function, which allowed them to increase the diagnostic accuracy from just one-third to one-half of all cases to 84%.
This multi-omics approach can lead to developing a strategy whereby patients receive a correct diagnosis earlier on. The earlier a diagnosis is given, the higher the chances for patients to receive the correct treatment.
How can MMA Therapy be Improved with Modern Science?
The scientists found that MMA patients use an alternative energy source to help deal with the fact that a vital enzyme is defective. However, in patients, this alternative energy source usually is not able to sufficiently compensate for the energy loss. In in vitro experiments with patient cells, the researchers succeeded in boosting energy production to near-normal levels with such an alternative energy source.
While these experiments provide hope, further research is required to determine if such innovative strategies can apply in animal models and find feasible solutions for patients. The researchers also launched a new interdisciplinary project, SwissPedHealth, co-funded by PHRT and the Swiss Personalized Health Network (SPHN), to increase diagnostic effectiveness and extend the multi-omics approach to other genetic diseases.
In conclusion, MMA is a rare genetic disorder that can cause severe illnesses for individuals affected by it. Still, scientists worldwide are dedicated to identifying the underlying mechanisms of the disease and providing patients with appropriate therapies. The multi-omics approach has proved to be a promising tool for a more accurate diagnosis of MMA and to find viable methods for treating patients. As research continues to expand, this rare disease may one day pave the way for new discoveries that could change the way genetic disorders are managed.
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