Janelly’s Journey

Photo by Daniel Dubois

Janet Amador and Salvador Martinez dressed 6-month-old Janelly Martinez-Amador for a professional photo shoot. The ventilator tubes and intravenous lines keeping their daughter alive in the neonatal intensive care unit were temporarily hidden by a tiny pink dress, pink ruffled socks and a matching pink and yellow daisy-shaped pacifier in her mouth.

 

With no cure or treatment available for this fragile infant’s rare disease, the photo was possibly going to be her last, a keepsake for her parents when she passed. Janelly was born with practically no bones, and the delicate traces of bones she did have were disappearing. Nobody knew how long she might live.

“She was becoming smaller and more fragile and weaker,” said Janet. “We would carry her on a pillow because we couldn’t carry her in our arms. Her body was almost like liquid.”

Doctors at Monroe Carell Jr. Children’s Hospital at Vanderbilt diagnosed Janelly at age 3 months with a rare genetic disorder called hypophosphatasia (HPP), a metabolic disease that affects the development of bone and teeth. An abnormal enzyme in the genes causes the bones to become soft because they can’t absorb important minerals such as calcium and phosphorus, increasing the risks for pain, broken bones and bone deterioration.

HPP affects about one in 100,000 babies born in the United States. While there are varying degrees of severity, the most severe forms of HPP occur before birth and early infancy. More than half of babies born with the disease don’t survive beyond their first birthday. Janelly had the most severe form.

“In HPP patients, the bone is continually breaking down and no new bone is made. Calcium levels are extremely high in the body because of the inability to absorb calcium, often leading to kidney stones,” said Jill Simmons, M.D., an endocrinologist at Children’s Hospital and part of Janelly’s care team.

At age 8 months, Janelly’s parents took her home from Children’s Hospital where she would live on a ventilator in a makeshift intensive care unit her father had created for her in the family living room. That’s where they would wait—but what they were waiting for wasn’t exactly known.

“Janelly was coming home to wait for the moment,” said Amador. “There was nothing anyone could do. We asked God that he wouldn’t take her from us, and said that we were going to fight, and fight with everything we had. Something had to happen to save Janelly’s life.”

 

Waiting for ‘something’

Something did happen to save Janelly’s life. But that “something” wasn’t one simple thing, person or moment. In addition to her family’s strong faith, Janelly has been nurtured by a complex care team at Vanderbilt that spans more than a dozen departments and medical divisions. After participating in an experimental drug therapy and clinical trial that began in 2009, Janelly celebrated her 7th birthday in May.

“Imagine your child laying all the time in bed, not being able to lift herself, not being able to move herself,” said Salvador Martinez referring to his daughter about four years ago. “The treatment has worked very well but it has been a compilation of doctors, nurses, assistants, everyone that has been a part of her care that has helped her make a meaningful recovery.”

The journey has been long and arduous. Janelly’s first test of survival came even before birth, before anyone knew she was ill. Many children diagnosed with the life-threatening form of HPP don’t survive the birth process. Their bone structure isn’t strong enough to make it through the birth canal and the result is frequently fatal.

But at 37 weeks of pregnancy, Janet Amador suffered appendicitis. Doctors decided to deliver her baby girl, Janelly, via cesarean section. Janelly weighed just over 5 pounds at birth in May 2006.

After failing to grow and gain weight by 3 months of age, Janelly’s parents sought help from her community pediatrician. Doctors initially thought she might have cancer and referred her to Children’s Hospital. With a thorough blood analysis, endocrinologists at Children’s Hospital diagnosed her with HPP.

Left: Paul Moore, M.D. Center: Jill Simmons, M.D. Right: Adriana Bialostozky, M.D.

Paul Moore, M.D., director of the Division of Pediatric Allergy, Immunology and Pulmonary Medicine, who has been part of Janelly’s care team since the beginning, had never seen a case this severe.

“Early on folks recognized there were differences in her skeletal structure that were impacting her ability to breathe,” said Moore, associate professor of Pediatrics and Pharmacology. “In Janelly’s case, her lungs were not able to provide the support for her to breathe adequately because her chest wall did not develop properly. The ribs literally disappeared from her X-ray. By 6 months of age, she was admitted to the intensive care unit and required mechanical ventilation to assist her breathing.”

The X-rays of Janelly’s body seemed to defy science and defy understanding, including among the medical community. Early images show thin, barely visible bones. With each new radiograph, the bone structure became replaced by dark shadows of nothing—in her chest, in her head and in her arms and legs.

Doctors have described Janelly’s body, only skin covering organs in her early years, as floppy and elastic.

“If you look at her X-ray from about 1 year of age, it is the most striking X-ray in the world,” Moore recalls. “You wonder, ‘where are the ribs on this child?’ Everyone who looked at her X-ray didn’t understand how this could be. We think about bone development in the arms and legs—she couldn’t walk or grasp anything with her hands, but sometimes we forget how important the chest wall and the ribs are just to maintain life.”

In fact, most children who suffer from severe HPP die from compromised respiratory function. When Janelly went home from the ICU at age 8 months, her parents were determined to keep her healthy and safe.

“This family was remarkable in the faith that they demonstrated that they would do whatever they could to provide for her care at home until a cure or treatment was available,” continued Moore.

“They kept her so healthy that when the drug became available she had no additional complications. She was incredibly healthy despite how dependent she was on technology.”

Janelly required round-the-clock care at home, with her parents suctioning her ventilator and tracheostomy, which had to be kept clean to avoid infection. A feeding tube kept her nourished with a low-calcium diet. The calcium her body couldn’t absorb converted to painful kidney stones.

She didn’t grow. She couldn’t move. She had regular visits with her Vanderbilt physicians. Her parents kept in constant contact with her care team, seeking answers to questions and researching her illness whenever possible.

“She was doing nothing other than lying on her back,” said Simmons. “She could not move against gravity.”

 

It was beautiful

Two years after her parents took her home from the ICU, they got a call from a Vanderbilt endocrinologist that there was a new experimental drug therapy for patients with HPP, but he warned there could be risks.

“She could die,” Janet Amador recalls hearing. “But we had faith that this experiment was going to work.”

That was in 2009, when Janelly became one of 11 children, age 3 and younger, to participate in a clinical trial (see sidebar on page 24) to receive an enzyme-replacement drug therapy, asfotase alfa, for the life-threatening form of HPP. The medicine had been developed by Enobia Pharma Corp of Canada, which has since been acquired by Connecticut-based Alexion. She had among the worst case of the group. Her baseline X-ray showed no visible bone.

She was about 2 years and 9 months old when the study began, but looked more like a newborn infant, barely weighing 19 pounds and 23 inches tall.

“If you saw her in 2009 and see her now, it’s not the same Janelly,” said Janet. “She used a respirator, an oxygen mask—many machines to help her breathe. She was just like an object lying there.”

Photo by Daniel Dubois

The treatment required Janelly and her parents to travel to Children’s Hospital three times a week, for at least two hours each visit, while she received injections of the asfotase alfa, while her blood pressure and liver enzymes were monitored. They did that for a year. Then, Janelly was able to start receiving the injections at home—also three times a week.

About eight months into the treatment, Janelly’s parents felt her fingers—which had been completely soft and boneless—and they could feel traces of developing bone. Her head also began to develop bone. At 18 months of therapy, X-rays showed for the first time visible development of her rib cage.

“It was beautiful,” said Adriana Bialostozky, M.D., assistant professor of Pediatrics at Vanderbilt and Janelly’s primary care physician, about those first X-rays. “It was an amazing thing to see a disease where you knew there was very little chance and then there was a drug that she was responding to. And she entered the trial very late for her age. For us to see her rib cage and the bones develop is amazing. That is what most of these kids die from (not having).”

Janelly’s parents believed if they hoped and waited long enough, the answer would come.

“We were so happy,” said Janet. “We knew—we knew—it was going to work. It was very slow, the process, but we were aware she was very severe, very advanced in her illness. But thank you to God we have her here with us, thank you to the doctors of Vanderbilt that fought with us.”

Moore said this is a representation of the best of what Vanderbilt has to offer in terms of complex care for a child who was so dependent on technology for such an extended period of time. “It also demonstrates a partnership that needs to exist between families and providers at the hospital when children are so critically ill. Janelly’s success is a real testament to a family who never gave up hope.”

Her toddler-like size at age 7 is still almost unfathomable. But she wasn’t supposed to live as an infant, let alone grow, especially since no trace of bone could be seen on X-rays just four years ago.

“This is why we get into medicine in the first place—to truly make a difference in the life of a child,” said Simmons. “To go from no bones to bones—that’s the most impressive thing I have seen as a physician. It’s incredible.”

 

– by Christina Echegaray