Scrolling Headlines:

: Nineteen turnovers sink UMass men’s basketball in loss to Fordham Saturday -

January 21, 2017

UMass men’s basketball falls to Fordham behind strong defensive effort by the Rams -

January 21, 2017

UMass hockey can’t take advantage of strong start in 6-1 loss to Boston College -

January 21, 2017

High-powered Eagles soar past UMass -

January 21, 2017

UMass women’s basketball suffers disappointing loss to St. Bonaventure at Mullins Center Thursday -

January 19, 2017

REPORT: Tom Masella out as defensive coordinator for UMass football -

January 19, 2017

Zach Lewis, bench carry UMass men’s basketball in win over St. Joe’s -

January 19, 2017

UMass women’s basketball handles Duquesne at home -

January 16, 2017

UMass men’s basketball’s late comeback falls short after blowing 15-point first-half lead -

January 15, 2017

UMass hockey outlasted at home against No. 6 UMass Lowell -

January 14, 2017

Hailey Leidel hits second buzzer beater of the season to give UMass women’s basketball win over Davidson -

January 13, 2017

UMass football hosts Maine at Fenway Park in 2017 -

January 12, 2017

UMass men’s basketball snaps losing streak and upsets Dayton Wednesday night at Mullins Center -

January 11, 2017

UMass women’s track and field takes second at Dartmouth Relays -

January 10, 2017

UMass hockey falls to No. 5 Boston University at Frozen Fenway -

January 8, 2017

UMass professor to make third appearance on ‘Jeopardy!’ -

January 8, 2017

UMass women’s basketball suffers brutal loss on road against Saint Joseph’s -

January 7, 2017

UMass men’s basketball drops thirds straight, falls to VCU 81-64 -

January 7, 2017

UMass men’s basketball drops tightly-contested conference matchup against George Mason Wednesday night -

January 4, 2017

Late-game defense preserves UMass women’s basketball’s win against rival Rhode Island -

January 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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