Her ribs disappeared on X-rays. But a new drug regenerated her skeleton.
Janet Amador and Salvador Martinez dressed 6 month old JanellyMartinez-Amador for a professional photo shoot.The breathing tubes and IV lines that kept her daughter alive in the NICU were concealed by a tiny pink dress, frilly socks and a matching pink and yellow pacifier in her mouth.
With no cure or treatment available for this fragile infant's rare disease, the photo would potentially be her last, a keepsake for her parents when she died. Janelly was a baby with almost no bones, and the faint traces of bones she had disappeared. Nobody knew how long she would live.
"She got smaller and more fragile and weaker," Janet said. "We carried her on a pillow because we couldn't carry her in our arms. Her body was almost like liquid.”
doctors atMonroe Carell Jr. Children's Hospital in Vanderbiltdiagnosed Janelly at the age of 3 months with a rare genetic disorder called hypophosphatasia (HPP), a metabolic disease that affects the development of bones and teeth. An abnormal enzyme in the genes causes bones to become weak because they cannot absorb important minerals such as calcium and phosphorus. People with HPP are at high risk of pain, fractures, and bone loss.
HPP affects about one in 100,000 babies born in the United States. There are different degrees of severity, and the worst forms occur before birth and in early infancy. More than half of babies born with the disease do not survive their first birthday. Janelly was in the most severe form.
“In HPP patients, bone is continuously degraded and no new bone is formed. Calcium levels in the body are extremely high due to the inability to absorb calcium, which often leads to kidney stones," he saidJill Simmons, M.D., an endocrinologist at Children's Hospital and part of Janelly's nursing team.
When she was 8 months old, Janelly's parents brought her home from Children's Hospital. She was living on a ventilator in a makeshift intensive care unit that her father set up in the family living room. There they would wait. But what they were waiting for was not exactly known.
"Janelly wanted to come home to wait for the moment," Amador said. “There was nothing anyone could do. We asked God not to take them away from us and said we would fight and fight with everything we had. Something had to be done to save Janelly's life.”
waiting for something'
Something happened to save Janelly's life. But that "something" wasn't a simple thing, person, or moment. In addition to her family's strong beliefs, Janelly was nurtured by a complex team of caregivers at Vanderbilt, spanning more than a dozen departments and medical departments. Janelly celebrated her 10th birthday in May 2016 after participating in an experimental drug therapy and clinical trial that began in 2009.
"Imagine your child lies in bed all the time, can't pick himself up, can't move," said Salvador Martinez, referring to his daughter's condition in 2009. "The treatment worked very well, but it was an assemblage of doctors, nurses, assistants — everyone who was a part of her care and helped her achieve a meaningful recovery.
The journey was long and arduous. Janelly's first survival test came before she was born, before anyone knew she was ill. Many children diagnosed with the life-threatening form of HPP do not survive delivery. Their bone structure is not strong enough to make it through the birth canal, and the result is often fatal.
But at 37 weeks pregnant, Janet Amador suffered appendicitis. Doctors decided to give birth to Janelly via cesarean section. She weighed just over 5 kg at birth.
When Janelly was not growing and gaining weight at the age of 3 months, her parents sought help from her local pediatrician. Doctors initially thought she might have cancer and referred her to Children's Hospital. With a thorough blood analysis, endocrinologists (doctors who specialize in glands and hormones) at Children's Hospital diagnosed her with HPP.
Paul Moore, MD,The director of the Department of Pediatric Allergy, Immunology and Pulmonology, who has been part of Janelly's treatment team from the start, had never seen a case this serious.
"Early on, people realized that there were differences in their skeletal structure that affected their ability to breathe," said Moore, associate professor of pediatrics and pharmacology. "In Janelly's case, her lungs were unable to allow her to breathe adequately because her chest wall had not developed properly. The ribs literally disappeared from her x-ray. At the age of 6 months she was admitted to the intensive care unit and required mechanical ventilation to support her breathing.”
The X-rays of Janelly's body appeared to defy science and understanding, including within the medical community. Early images show thin, barely visible bones. With each new X-ray, the bony structure was replaced by dark shadows of nothing—in her chest, in her head, and in her arms and legs.
Doctors have described Janelly's body, which in her early years was skin-covered organs, as limp and elastic.
"If you look at her x-ray from about a year ago, it's the most conspicuous x-ray in the world," Moore recalls. "You're like, 'Where are this kid's ribs?' Anyone who looked at her x-ray couldn't understand how that could be. We think about the bone development in her arms and legs – she couldn't walk or grab anything with her hands, but sometimes we forget how important the chest wall and ribs are just to sustain life.”
In fact, most children who suffer from severe HPP die because they cannot breathe properly. When Janelly returned home from intensive care at the age of 8 months, her parents were determined to keep her healthy and safe.
"This family has been remarkable in believing that they have shown that until a cure or treatment becomes available, they would do whatever it takes to provide for her at home," Moore continued. “They kept her so healthy that when the drug became available she had no further complications. She was incredibly healthy despite being addicted to technology.”
Janelly required round-the-clock care at home, with her parents vacuuming her ventilator and tracheostomy, which needed to be kept clean to prevent infection. A feeding tube put her on a low-calcium diet. Calcium that her body couldn't absorb turned into painful kidney stones, something to be avoided.
Janelly has not grown. She couldn't move. She had regular visits to her Vanderbilt doctors. Her parents were in constant contact with her care team, seeking answers to questions and researching her illness whenever possible.
"All she did was lie on her back," Simmons said. "She couldn't move against gravity."
'It was wonderful'
Two years after her parents brought her home from intensive care, they received a call from a Vanderbilt endocrinologist that there was an experimental new drug therapy for patients with HPP, but he warned of risks.
"She could die," recalls Janet Amador. "But we had faith that this experiment would work."
That was in 2009 when Janelly, as one of 11 children ages 3 and under, was enrolled in a clinical trial to receive an enzyme replacement drug called asfotase alfa to treat life-threatening HPP. The drug was developed by Canadian Enobia Pharma Corp. developed, which has since been acquired by Connecticut-based Alexion. Janelly had one of the worst cases in the group. Her baseline x-ray showed no visible bone.
She was around 2 years and 9 months old when the study began but looked more like a newborn child, standing just 23 inches tall and weighing barely 19 pounds.
"If you saw her in 2009 and you see her now, it's not the same Janelly," Janet said. “She was on a ventilator, an oxygen mask — lots of equipment to help her breathe. She was like an object lying there.”
Treatment required Janelly and her parents to go to Children's Hospital three times a week for at least two hours to get asfotase alfa injections. They did that for a year. Then Janelly could get the shots at home, also three times a week.
About eight months after the treatment, Janelly's parents felt their fingers - which had been completely soft and boneless - and they could feel traces of bone development. Her head also began to develop bones. After 18 months of therapy, X-rays showed visible development of her chest for the first time.
"It was beautiful," he saidAdriana Bialostozky, MD, assistant professor of pediatrics at Vanderbilt and Janelly's family doctor, on those first X-rays. "It was amazing to see a disease where you knew there was very little chance and then there was a drug that responded to it. And she entered the process very late for her age. It's amazing for us to see how her rib cage and bones are developing. Most of these kids die from it (they don't have it).”
Janelly's parents believed that if they hoped and waited long enough, the answer would come.
"We were so happy," said Janet. "We knew - we knew - it would work. It was a very slow process, but we were aware that her illness was very serious and very advanced. But thank God we have her here with us, thanks to the doctors at Vanderbilt who fought with us.”
According to Moore, this is a representation of the best Vanderbilt has to offer in terms of the complex care of a child who has been so dependent on technology for so long. “It also shows a partnership that needs to exist between families and providers in the hospital when children are so seriously ill. Janelly's success is a true testament to a family that has never given up hope."
Her toddler-like size at the age of 7 was still almost unfathomable. But as an infant she was not supposed to live at all, let alone grow.
"That's why we get into medicine in the first place: to really make a difference in a child's life," Simmons said. "Going from zero to bones - that's the most impressive thing I've seen as a doctor. It's incredible."
Editor's Note: Since this article was originally published in Vanderbilt's Hope Magazine in 2013, Janelly has continued to respond well to treatment. The experimental drug, which regrows her bones, was approved by the FDA in October 2015, and patients with all forms of childhood HPP can now receive it, Simmons says. Janelly has inspired children and adults worldwide suffering from various forms of HPP, and her story has raised awareness of the expertise and comprehensive care that pediatric and adult physicians at Vanderbilt University Medical Center and Children's Hospital are able to provide to treat disease.This postprovides an update on these efforts.
Christina Echegarayis Information Officer for Vanderbilt University Medical Center.
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