UW News

January 19, 2018

University Faculty Lecture to highlight screening newborns for genetic diseases

UW News

On the evening of Jan. 23, one University of Washington scientist will share his passion for what he calls “the chemistry of saving babies.” For this year’s University Faculty Lecture, UW professor Michael Gelb, the Boris and Barbara L. Weinstein Endowed Chair in Chemistry and adjunct professor of biochemistry, will discuss the science behind screening newborns for treatable — but rare — genetic diseases.

Michael_GelbGelb studies enzymes. These are the minute but busy protein catalysts within our cells that perform a variety of tasks — such as breaking down food, shuttling away toxins and building up new molecules to keep our cells, organs and bodies in good working order.

But sometimes, due to random genetic mutation, these enzymes struggle to perform their proper roles, causing rare and often fatal diseases in babies and children. Gelb and his colleagues have worked to develop screens that can accurately test in babies how well certain types of enzymes are functioning. Using only a drop of blood, these tests can identify newborns who will need treatment, saving their lives and giving them a robust start.

Ahead of his lecture, Gelb sat down with UW News to discuss his research.

What types of diseases have you been working on to develop newborn screening procedures?

MG: They’re called lysosomal storage diseases. The lysosome is a cellular compartment in which enzymes break down large molecules and recycle their components for use by the cell. Each type of lysosomal storage disease is caused by a deficiency in a different lysosomal enzyme. The deficiency disrupts biochemical pathways and cellular metabolism — eventually leading to disease.


What are the advantages to screening newborns for these rare diseases?

MG: The main advantage is treatment. It is valuable to begin treatment for these diseases early — before the symptoms of these enzyme deficiencies emerge that would negatively impact development of these children or threaten their lives. This is really the chemistry of saving babies.


How does a tiny drop of blood tell us whether these enzymes are working properly?

MG: These enzymes are present in blood. So we use dried blood spots — which is something that can be easily collected from a newborn in a hospital or clinic. And we developed a way to use mass spectrometry to screen for how well these different lysosomal storage enzymes are working. Mass spectrometry was a very promising approach because you can easily adapt it to measure the function of many types of enzymes at once in a clinical setting.


What led you to pursue this line of research in the first place?

MG: I first got the idea in the mid-1980s, when my wife was pregnant with our second child and underwent amniocentesis. I asked the nurses what they were checking for, and they said just a few conditions such as Down syndrome. But I had this background in chemistry, and I was studying enzymes. So I thought, “Why not test for enzymes?” I’d also recently seen the film “Lorenzo’s Oil,” which is about a boy with a rare genetic disease. Those experiences planted the idea in my head, though I didn’t immediately pursue newborn screening for enzyme deficiencies.


Then what ultimately led you to develop tests for enzyme functions at birth?

MG: Well, I eventually met Ron Scott here at the UW, who is a professor of pediatrics and an expert in rare genetic diseases. I talked to him about my idea to develop a newborn screen for enzyme deficiencies. He liked it. I then brought in my colleague Frank Tureček, a fellow UW professor of chemistry and an expert on mass spectrometry. The three of us form a good team: I’m the chemist, Ron’s the clinician and Frank’s the mass spectrometry expert.


Many lysosomal storage diseases exist. How do you and your colleagues decide which ones to target with your tests?

MG: Well, we want these tests to be informative and useful for families. So, we’ve chosen to focus on diseases for which there are treatments available.


Once you develop an accurate screen for a disease, how could it be incorporated into the standard panel of newborn tests?

MG: In the United States, individual states mandate their own array of tests for newborn babies. There are federal guidelines — but they are recommendations. It’s ultimately up to the states to decide. So, to get a particular test adopted in your state, there are two basic routes: One is to advocate for the test to be incorporated into the recommended federal guidelines, which are set up through the congressional Newborn Screening Saves Lives Reauthorization Act of 2014. The other route is to simply lobby an individual state government directly. Tests that we’ve developed for two lysosomal storage diseases — Pompe disease and MPS I — have gone through the federal route. A test for another lysosomal storage disease, Krabbe disease, was first adopted by some localities on a state-by-state basis. Through these approval pipelines, newborns are currently screened for dozens of diseases, most of them rare. In Washington state, for example, out of 80,000 babies born this year, screening for one enzyme deficiency may identify four or five babies who need immediate treatment, and about a dozen who need monitoring for possible future disease. But that’s as many as 20 lives saved or improved each year in Washington state, and 20 families spared suffering.


Where would you like to see the field of newborn screening go in the future?

MG: I would like to see every severe genetic disease — one that causes massive suffering or is life-threatening, but is also treatable — added to the list. That requires doing the necessary experiments to develop screens for these diseases, and the trials needed to show that those tests are accurate. That way, these screens become a source of hope for families.


The 42nd annual University Faculty Lecture will be held at 7:30 p.m. Jan. 23 in Kane Hall, room 130.