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Meg Colleran dominates as UMass softball tops Saint Joseph’s, advances in A-10 tournament -

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Rain keeps UMass softball from opening tournament play; Minutewomen earn A-10 honors -

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Former UMass football wide receiver Tajae Sharpe accused of assault in lawsuit -

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Justice Gorsuch can save the UMass GEO -

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Minutemen third, Minutewomen finish fifth in Atlantic 10 Championships for UMass track and field -

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UMass women’s lacrosse wins A-10 title for ninth straight season -

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Dayton takes two from UMass softball in weekend series -

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Towson stonewalls UMass men’s lacrosse in CAA Championship; Minutemen season ends after 9-4 loss -

May 6, 2017

Zach Coleman to join former coach Derek Kellogg at LIU Brooklyn -

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UMass men’s lacrosse advances to CAA finals courtesy of Dan Muller’s heroics -

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On campus: The liberal assault on free speech -

May 4, 2017

Biochemistry department develops new understanding of Fabry disease

The University of Massachusetts department of biochemistry has given the medical community an important key in the understanding and treatment of the rare genetic disorder Fabry disease. Dr. Scott C. Garman and a team of researchers have published new findings on the causes of Fabry disease in the Journal of Biological Chemistry.

Fabry disease is a rare genetic disorder caused by a mutation in an enzyme called alpha-galactosidase (alpha-GAL), which inhibits the enzyme’s ability to break down a lipid called globotriaosylceramide (GL-3 or GB-3). The accumulation of GL-3 usually begins in childhood, called early-onset or classic Fabry, but there have been some cases where patients showed no symptoms until adulthood, or late on-set.

Symptoms of Fabry disease can include, but are not limited to: a burning or tingling in the hands and feet, skin lesions, high blood pressure, cloudy corneas, heart anomalies, fatigue and a lack of or (in rare cases) excessive sweating, according to the Fabry disease support Web site fabry.org. If the disease is left untreated it can be fatal. The extreme build-up of GL-3 leads to kidney failure, heart disease, heart failure and stroke.

For many people living with Fabry disease, the diagnosis is a shock. People suffering from early-onset Fabry disease can go for years suffering with burning pain in the hands and feet without anyone noticing something is wrong until years later, when their kidneys begin to fail.

For many people, being diagnosed with Fabry disease has severely limited their activity. Some are unable to maintain vigorous physical activity of any kind because of their body’s inability to sweat, causing high fevers. People with kidney failure may need to stay on renal dialysis for the rest of their lives. For people living with Fabry disease there are several medications prescribed to manage the symptoms.

The treatment for Fabry disease is enzyme replacement therapy and is extremely expensive. The severity of symptoms and the toll it takes on a person’s life vary from case to case, but something all cases share is the impact the diagnosis has on the patient’s family. If one person in a family has it, there’s a better-than-average chance that someone else does too.

 The mutation in the alpha-GAL enzyme is passed on in families via the X chromosome, and not everyone who carries the gene develops the disease. Fabry disease is more common in men who inherit the gene from their mothers. A man with Fabry disease can pass it on to his daughters, but not his sons. A woman with Fabry disease has a 50 percent chance of passing it on to her children.

Fabry disease is still quite rare and has been detected in approximately 1 in 40,000 people, but the numbers are increasing. According to UMass researcher Dr. Garman, the numbers could be as high as 1 in 4,000.

“Frequency is going up because methods of detection are getting better,” he said.

Dr. Garman, of the department of biochemistry, headed a research project which has made an enormous leap forward in the understanding of the mutation in the alpha-GAL enzyme which leads to the development of Fabry disease, along with other lysosomal storage diseases.

Starting in 2004, Garman led a research team made up of two UMass graduate students, Abigail Guce and Nathaniel Clark, technician Eric Salgado and several colleagues from research institutes in Sweden and Russia. Garman said he mostly supervised the work and gave a great deal of research’s credit to the students in the lab.

“They are the ones who are doing the work,” said Garman.

The purpose of the research was to essentially map the structure and movement of the alpha-GAL enzyme atoms in order to pinpoint the mutations which lead to Fabry disease. The researchers in Sweden and Russia worked together to create a synthetic molecule mimicking the structure and movement of the alpha-GAL enzyme. The difference was that the synthetic enzyme contained a substrate called para-nitrophenyl-alpha-galactose (pNP-alpha-Gal) which allowed the team at UMass to slow and stop the motion of the molecules in order to create three-dimensional images of each stage in the enzyme’s function.

The images created by Garman’s team have proven to be instrumental in furthering the understanding of how this enzyme works. This is important not only to clinical research of Fabry disease, but in other research as well. The process occurring in the alpha-GAL enzyme “applies to a huge number of other proteins,” said Garman. There are roughly 2000 other proteins which perform a similar function, not only in humans but in plants and animals, as well.

Because of the research performed by Garman’s team, the medical community now has a better understanding of the structure of the alpha-GAL enzyme, which could be critical to advancing the knowledge and treatment of debilitating conditions like Fabry disease.

Ellie Goerlach can be reached at egoerlac@student.umass.edu

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