Breakthrough Blood Test Accelerates Diagnosis of Rare Genetic Disorders

A groundbreaking blood test has been developed that significantly enhances the speed of diagnosing rare genetic disorders in infants and children. This innovative method was unveiled at the recent annual conference of the European Society of Human Genetics.

Despite their classification as rare, there are over 7,000 distinct genetic disorders associated with mutations in more than 5,000 genes, impacting an estimated 300 million people globally. Currently, about 50% of patients suspected of having a rare disease do not receive a definitive diagnosis. Traditional testing methods are often slow, focused on specific conditions, and may lack sensitivity, leading to prolonged periods of uncertainty and invasive testing for families.

Dr. Daniella Hock, a Senior Postdoctoral Researcher at the University of Melbourne, Australia, has spearheaded the development of a blood-based technique that analyzes thousands of proteins in a single untargeted test. This novel approach sequences proteins instead of genes, yielding insights into how genetic mutations can affect protein function and contribute to disease.

The test's versatility allows it to potentially diagnose thousands of different genetic conditions and even identify new disorders by providing evidence that can confirm the linkage between genetic changes and disease manifestations.

One of the test's key advantages is its speed and minimal invasiveness, requiring merely 1 ml of blood from infants and delivering results in under three days for those in acute care settings. When blood samples from parents are included, referred to as trio analysis, this method enhances the ability to distinguish between carriers of genetic mutations and affected individuals.

A swift molecular diagnosis can lead to timely access to relevant treatments, if available, and provide families with clarity regarding the prognosis. Additionally, having a confirmed diagnosis opens up reproductive options to prevent similar genetic conditions in future pregnancies through prenatal or preimplantation genetic testing. For healthcare systems, this comprehensive test could streamline the diagnostic process, reducing costs by minimizing the need for multiple targeted tests and enabling earlier intervention.

Research conducted in collaboration with the Melbourne School of Population and Global Health indicates that implementing this proteomic test in clinical environments would incur costs comparable to current diagnostic methods for rare mitochondrial diseases, while offering the added benefit of diagnosing a broader array of conditions.

The new test can detect over 8,000 proteins found in peripheral blood mononuclear cells (PBMCs), accounting for more than 50% of known Mendelian and mitochondrial disease genes, while also facilitating the discovery of new genetic disorders.

Researchers anticipate that this innovative testing method will become a standard part of the diagnostic process for rare and other genetic diseases in clinical laboratories. The ability to utilize such a small blood volume and obtain reliable results quickly has proven transformative for affected families. Moreover, the implementation of trio analysis has significantly improved the confidence in differentiating between carriers and affected individuals, surpassing initial expectations.

Professor Alexandre Reymond, chair of the conference, remarked on the potential of non-invasive, agnostic approaches like genome sequencing and protein analysis to expedite diagnoses in the future and to solve previously unresolvable cases, thereby assisting families around the globe.