Researchers expect their test to reduce diagnostic time in clinical settings and help identify carriers of the diseases

Clinical laboratories have always been at the forefront of helping families battle rare diseases. But such testing is sometimes invasive and expensive. Now there’s a new blood test that is minimally invasive and rapidly detects thousands of rare genetic diseases in infants and children using a mere 1ml of blood.

Developed at the University of Melbourne and Murdoch Children’s Research Institute in Australia, the test rapidly detects abnormalities using proteomics to simultaneously analyze the pathogenicity of thousands of gene mutations that cause rare genetic illnesses.

The single-drop blood test sequences proteins present in the genes rather than the genes themselves to discover how genetic changes within those proteins affect function and lead to disease. According to the scientists, the test is cost-effective, potentially eradicates the need for other functional tests, and may be applicable to thousands of different diseases. Results of the test are typically available within three days, providing patients with earlier access to any available treatments.

“A recent study carried out in collaboration with the Melbourne School of Population and Global Health revealed that implementing our test in a clinical setting would have a similar cost to that of the current test used to diagnose rare mitochondrial disease, with the advantage that our test can potentially diagnose thousands of other diseases,” said the study’s co-author, Daniella Hock, PhD, a research fellow in clinical proteomics in the department of biochemistry and pharmacology at the University of Melbourne, in a news release.

The researchers presented their findings at the annual European Society of Human Genetics conference in Milan, Italy, and also in the journal Genome Medicine titled, “Untargeted Proteomics Enables Ultra-Rapid Variant Prioritization in Mitochondrial and Other Rare Diseases.”

“Our new test can identify more than 8,000 proteins in peripheral blood mononuclear cells covering more than 50% of known Mendelian and mitochondrial disease genes, as well as enable us to discover new disease genes,” said Daniella Hock, PhD, research fellow in clinical proteomics, department of biochemistry and pharmacology at the University of Melbourne, in the news release. (Photo copyright: Mito Foundation.)

Identifying Disease Carriers

The researchers also performed blood analysis on the parents to help identify the carriers of genetic illnesses and possibly develop reproductive methods to avoid the occurrence of those diseases in future pregnancies.

“When the test is also performed on blood samples from parents we call it trio analysis. In recessively inherited conditions, this helps considerably in differentiating between carriers, who only have one copy of the defective gene, and the affected individual, who carries two copies,” Hock said. “Moreover, the use of familial samples for trio analysis greatly improves the differentiation between carrier and affected individuals with higher confidence, and that has exceeded our initial expectations. We believe that the use of this test in clinical practice will bring considerable benefits to patients, their families, and healthcare systems by reducing the diagnostic time.”

Getting the Right Diagnosis

There are more than 7,000 types of categorized rare diseases which affect approximately 300 to 400 million people worldwide. These diseases are caused by genetic mutations that exist in more than 5,000 known genes. The new test focuses on rare genetic illnesses known as monogenetic disorders, such as cystic fibrosis and mitochondrial disease, that are caused by a single gene alteration or mutation.

According to the National Organization for Rare Disorders, 25 to 30 million Americans are living with a rare disorder. A condition is categorized as rare if it affects less than 200,000 individuals.

Global Genes states on its website that 400 million people worldwide suffer from a rare disease and half of those diagnosed are children. It also states that 80% of those diseases are genetic and 95% of rare diseases lack a treatment approved by the US Food and Drug Administration.

“One of the hardest things for patients with rare diseases is getting the right diagnosis,” said Sharon Barr, PhD, executive vice-president of biopharmaceuticals research and development at AstraZeneca Rare Disease, in an interview with STAT News.

On average, it takes about five years to accurately diagnose a rare disease patient. During that period, that patient sees various specialists, undergoes difficult tests, and potentially faces the wrong diagnosis, Barr said.

Initial results stemming from the new clinical laboratory test are encouraging, but more research and clinical trials are needed before the test can be used on a widespread level.                

—JP Schlingman