Rare metabolic diseases such as Tay-Sachs, Fabry and Gaucher syndromes are caused by enzyme deficiencies and typically have crippling, even fatal, consequences starting at very early ages. Now a team of University of Washington scientists has developed a relatively simple screening process to detect enzyme deficiencies in newborns that will allow treatment to begin before too much damage has been done.
"All of the damage from these diseases is permanent, so if you can start treatment early, in a few weeks or months, you can begin to minimize the damage," said Frantisek Turecek, a UW chemistry professor.
The technique uses a spot of blood drawn from a baby’s heel and dried on a paper card. A 2-millimeter section is punched out of the spot, then is rehydrated, the target enzymes are incubated and then measured using tandem mass spectrometry, a means of determining a substance’s chemical makeup and quantity. The sample can be screened for perhaps 15 enzyme deficiencies at the same time, and the entire process typically will take less than two days, Turecek said
So far the screening method has been effective in detecting seven diseases – Krabbe, Pompe, Niemann-Pick, Gaucher, Fabry, Tay-Sachs and Hurler syndromes – associated with enzyme deficiencies within structures called lysosomes, which break down large molecules in most cells.
In each of the diseases, babies typically are symptom free for the first few months to a year of life and then begin to show signs of the disease. The effects can appear gradually over many years or can accumulate rapidly, with the worst cases causing mental retardation, blindness and finally death by the age of 5 or 6. The diseases begin when a missing link – a deficient enzyme – in the lysosome’s biochemical chain causes waste material to accumulate in the cell.
"It’s like the garbage collectors have all gone on strike," Turecek said. "The garbage builds up, the cell struggles and eventually it dies."
The diseases are relatively rare, and typically the greatest risk lies with certain populations. Tay-Sachs, for instance, occurs most frequently in descendants of central and eastern European Jews, and about one in 30 American Jews carries the Tay-Sachs gene, an occurrence about 100 times greater than for other ethnic groups. Non-Jewish French-Canadians and Cajuns of Louisiana have a similarly elevated risk.
Some of the telltale symptoms can be very similar among all these diseases, making a medical diagnosis difficult, particularly early in life when the symptoms are not readily apparent. The new screening method will allow precise diagnosis very early, so newly developed pharmaceutical treatments can be administered in time to repair the break in the lysosome’s biochemical chain and stop further damage.
After an initial investment in mass spectrometry equipment, the new screening should have a relatively low cost, perhaps 5 cents per analysis for chemicals and materials, Turecek said. He estimates one tandem mass spectrometer could process 85,000 screenings a year, equivalent to the state of Washington’s annual birth rate.
The UW research team has been working toward a new screening method since 1998. It began using cultured skin cells but switched to blood samples three years ago. Other members of the research group are chemistry professor Michael Gelb, pediatrics professor C. Ronald Scott, chemistry graduate student Ding Wang and chemistry postdoctoral researcher Yijun Li. The work is supported by grants from the National Institutes of Health and Genzyme Corp. of Cambridge, Mass.
Turecek discusses the team’s work March 28 at the American Chemical Society national meeting during a session honoring Richard Caprioli, a Vanderbilt University biochemist who is receiving the society’s Field and Franklin Award for Outstanding Achievement in Mass Spectrometry.
Other diseases eventually can be added to those being screened for, Turecek said, and it could be possible to screen for even more with additional spectrometer runs for a given sample.
"These diseases are such a tragedy," he said. "If we can find them early enough to stop further damage, we can improve the quality of life for these kids."
Vince Stricherz | EurekAlert!
Novel PET tracer identifies most bacterial infections
06.10.2017 | Society of Nuclear Medicine and Molecular Imaging
Teleoperating robots with virtual reality
05.10.2017 | Massachusetts Institute of Technology, CSAIL
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
17.10.2017 | Life Sciences
17.10.2017 | Physics and Astronomy
17.10.2017 | Life Sciences