Sisters team up to fight rare genetic disorder: Boston Children’s leads LAL-D clinical trial

Walsh girls, Jr. Bridesmaids
(L-R) Maureen and Lauren Walsh

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Sisters Lauren and Maureen Walsh have smiles that light up a room and personalities to match.

Though they have very different interests—Maureen, 14, is an avid dancer and member of a high school dance team, and Lauren, 11, is a defensive player on a co-ed hockey team, the duo share one important mission: to conquer the genetic liver disorder lysosomal acid lipase deficiency (or LAL-deficiency).

In June 2012, the Walsh sisters were diagnosed with late-onset LAL-deficiency—a metabolic disorder in which the body does not produce enough of an enzyme responsible for breaking down fatty materials in the body. The condition, which typically prompts a build up of fat in the liver, spleen and other parts of the body, is rare and often difficult to detect.

For Lauren, who is more affected by the disorder, the signs and symptoms of LAL-deficiency emerged in October 2010 when she was 6 years old.

Walsh girls
Maureen (l) and Lauren (r)

“She was very ill with a lot of belly aches and general fatigue,” recalls her father Greg. “She wasn’t eating much and [was] not herself.”

Initially, Lauren’s local pediatrician believed the first-grader was battling a virus. But concern spiked as her symptoms persisted for several weeks. “She just wasn’t beating it,” her dad says.

Further evaluations showed Lauren’s liver was slightly enlarged, her cholesterol was elevated and her alanine aminotransferase (ALT) levels were above normal range—all pointing to liver damage.

Lauren’s parents, Greg and Susan, opted to call a specialist: Boston Children’s director of Hepatology, Maureen Jonas, MD.

Jonas monitored Lauren’s condition in hopes of pinpointing the cause of her abnormal liver function. Over time, Lauren showed physical improvements, but her levels continued to remain high. Jonas then recommended a liver biopsy.

The liver biopsy results

“The biopsy showed two important things: it showed a metabolic picture where it looked like it could have been a metabolic disease or enzyme deficiency. It also showed a lot of scar tissue,” Jonas recalls. “At that point, we knew we had more serious liver disease than anticipated.”

Based on test results and Jonas’ assessment, Lauren was referred to Edward Neilan, MD, PhD, and Boston Children’s Metabolism Program for metabolic and genetic testing.

An enzyme assay, a laboratory method of measuring enzyme activity, indicated Lauren had LAL-deficiency, and a genetic test revealed the specific gene sequences causing Lauren to have this disease. Lauren’s results also prompted the need to genetically test her siblings—Maureen and Gregory.

Maureen tested positive for the disease after her ALT levels were found to be abnormal. Gregory’s test showed he is a non-symptomatic carrier of the gene.

The quest to find LAL-deficiency treatment

Currently, there is no approved treatment for LAL-deficiency; however, Neilan and Jonas were determined to find a treatment option for Lauren and Maureen.

According to Neilan, previous attempts to treat LAL-deficiency in other patients included reducing dietary fat intake and/or using medications to lower blood cholesterol levels. However, this form of treatment did not seem to stop the slow-but-steady progression of the underlying liver disease.

“Once the LAL-deficiency diagnosis was made, we needed to see if there was a way of treating it,” Neilan says.

Leading the way in LAL-D research

With the approval and support of the Walsh family, Lauren and Maureen, along with a third Boston Children’s patient with LAL-deficiency, were enrolled in the first multi-center, enzyme- replacement clinical trial for LAL-D, with Neilan serving as the principal investigator for the trial at Boston Children’s.

The enzyme-replacement technology utilized in the clinical trial puts back the missing enzyme via intravenous infusion, and this, he says, “logically offers a more complete treatment.”

“We are so thankful for Dr. Jonas and Dr. Neilan for being so persistent and thorough with their research and care for all of our children,” says mom, Susan. “We would never had known about this disease had they not followed up and closely monitored Lauren’s elevated liver enzymes.”

Moving forward

teen-with-lal-deficiency
Maureen and Lauren with their care team

The girls undergo biweekly intravenous infusions and are treated and cared for by a team of Boston Children’s physicians, nurses and clinical staff.

The girls’ care team does far more than administer treatment. “All my nurses are kind and take very good care of me,” Lauren says.

Since the beginning of the clinical trial, the girls have made steady progress, Dad says.

“Their levels have greatly improved since they started the clinical trial. Maureen’s levels are in the normal range, and Lauren’s are a little above normal range but much improved,” he adds.

Lauren Walsh_Hockey 2
Lauren, defensive hockey player
Maureen_dancer
Maureen, dance team

Throughout the clinical trial, Lauren and Maureen have been indulging in the activities they cherish: dance, sports, hanging out with friends and most importantly—being kids.

“I am the world’s biggest fan of Boston Children’s Hospital. If we didn’t live where we live, the girls wouldn’t be receiving this kind of care.”

Learn more about Boston Children’s Division of Gastroenterology, Hepatology and Nutrition.