Hope for children with rare disorder

By Sandy Kleffman

OAKLAND — Two-year-old Amro smiles and chases the bubbles his father is blowing to help pass the time. The movie "Shrek" plays on a small television above his bed.

The pair are thousands of miles from their home in Palestinian territories, but this has become a familiar routine.

One day each week, Amro and Yaser Housheya spend several hours at Children's Hospital Oakland as Amro receives intravenous treatment for a rare condition known as mucopolysaccharidoses or MPS.

Two years ago, Housheya gave up his construction job and left behind his wife and four other children so that Amro could receive enzyme replacement therapy here.

MPS is a hereditary disorder that occurs when people lack an enzyme needed to break down a complex sugar as part of normal cell metabolism. In healthy people, the enzymes help recycle cellular waste.

But for people with MPS, the missing or insufficient enzyme prevents proper recycling. Sugar molecules remain stored in abnormal locations throughout the body, causing progressive damage.

Children's Hospital Oakland is the only site in the nation conducting a clinical trial of a treatment for infants with the unusual form of MPS that Amro has.

"I sacrificed for my son to come here," Housheya said in Arabic, speaking through an interpreter.

Amro's journey highlights the hope that many MPS patients and their families have placed in the latest therapies for the

It also illustrates the importance of early diagnosis, a theme that will be emphasized Thursday when Children's Hospital Oakland celebrates international MPS awareness day. Patients from throughout the region will gather at the Oakland hospital and at a similar event in Raleigh, North Carolina.

Housheya said he brought Amro to the United States because he did not want him to end up like his brother. Six-year-old Mohammad also has MPS. Without treatment, Mohammad's condition has irreversibly worsened.

"He does not move," Housheya said. "He just sits there. He doesn't recognize anyone. He doesn't speak. ... Because of lack of treatment in Palestine, I lost one son. I don't want to lose the other one."

MPS affects one in 25,000 children.

"It's such a rare disease that most people have never really come in contact with patients who have it," said Dr. Paul Harmatz, the gastroenterologist who is treating Amro.

"We hope we'll be able to identify these patients much earlier and bring them to therapy when we can have the most effect."

Scientists have identified seven types of the disorder. Amro has MPS VI or Maroteaux-Lamy syndrome, which occurs in one in 300,000 children.

Symptoms vary from one form of MPS to another, but may include short stature, coarse facial features, cloudy corneas, stiff finger joints, bone abnormalities, hearing impairment, heart disease and in some cases, mental retardation.

Some types of MPS, including the form Amro has, often lead to death before early adulthood. For other people, a normal life span can be possible.

As Amro chased bubbles on a recent Tuesday, Rodeo resident Annette Zubia sat nearby with her sons, 11-year-old Nicholas and 7-year-old DiAngelo. Both boys have MPS II or Hunter syndrome.

The family lived in a small town in New Mexico when Nicholas was young. He suffered numerous problems and stopped growing at 31/2, but they went to several doctors before they got a diagnosis.

A drug company paid to fly Nicholas and his mother from their new home in Las Vegas to Oakland each Tuesday for several years so he could receive enzyme replacement therapy. Eighteen months ago, the family moved to the East Bay to be closer to treatment for both boys.

"It's a devastating disorder to deal with, but knowing is the most important thing," Zubia said.

Elaprase, an enzyme replacement therapy developed by Shire Human Genetic Therapies, and weekly physical and occupational therapy, has markedly improved Nicholas, she said. Now a fourth-grader at Rodeo Hills Elementary School, Nicholas enjoys playing with his classmates, something he couldn't do before.

"He would get so tired that it wasn't fun," his mother said. "He couldn't keep up with the other kids. ... But now he's running and playing like a regular kid."

DiAngelo is having a harder time. He appears to have brain damage, is deaf in one ear and "really struggles," his mother said.

Amro receives an FDA-approved enzyme replacement therapy called Naglazyme created by Novato-based BioMarin Pharmaceutical. Previous studies have looked at its effectiveness in children ages 5 and older, but Children's Hospital Oakland is analyzing its effectiveness in infants younger than 1, Harmatz said.

Insurance companies will usually pay for such treatments, but it can cost $50,000 to $300,000 annually for a supply of the drug and some people exceed their insurance caps, Harmatz said. The treatment extends for the duration of a patient's life.

"It's not only the expense that's difficult — the issue is also the time involved," said Dr. Seymour Packman, a pediatrics professor at UCSF.

Enzyme replacement therapy takes several hours each week, affecting school and work, Packman said. While it can be very effective in slowing a patient's decline, some people react to the medication and everyone needs to be monitored closely, he said.

Packman co-directs the UCSF-Stanford Lysosomal Center, which treats many children with MPS.

UCSF is involved in clinical trials of a different approach: Instead of trying to replace the insufficient enzyme, it is exploring ways to make the enzyme that does exist in a patient's body more efficient or to increase its production.

Both Harmatz and Packman said physicians, physicians-in-training and the general public need to be educated about the symptoms of MPS so children can be diagnosed for early treatment. The state's newborn screening program does not check for MPS. Housheya is happy with Amro's progress, but he worries about what will happen in March 2009 when his visa expires and the clinical trial ends for his son. He fears he will not be able to get the enzyme replacement if he returns to home and that Amro will decline. The drug company paid for his trip to the United States and an apartment while he is here.

"I would like some type of solution so I could stay here in this country," Housheya said. "Amro is good. That's why I don't want him to get worse."

Amro's spinal column has begun to curve backward, a sign of the disorder, but Harmatz also is pleased with his progress.

"He's doing beautifully — just to see him up running and enjoying himself," Harmatz said. "It's just amazing how much he's grown up and how normal he is as a child at this point.

"His dad's a great father," he added. "It's a tribute to him how well Amro has done without his family and his mother."

Reach Sandy Kleffman at 925-943-8249 or skleffman@bayareanewsgroup.com.