Born with a Rare Condition, Little girl had to Grow New bonesOctober 21, 2015 by Christina Echegaray at MySouthernHealth / Republished at BuildingBones.org in February 2017
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 hidden by a tiny pink dress, ruffled 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 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 affecting 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. People with HPP are at high risk of pain, broken bones and bone deterioration. HPP affects about one in 100,000 babies born in the United States. There are varying degrees of severity, and the worst forms 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. When she was 8 months old, Janelly's parents took her home from Children's Hospital. She lived on a ventilator in a makeshift intensive care unit her father created 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 team of caregivers at Vanderbilt spanning 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 10th birthday in May 2016. "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's condition in 2009. "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 birth. 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 Janelly via cesarean section. She weighed just over 5 pounds at birth. When Janelly failed to grow and gain weight by 3 months of age, her 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 (doctors specializing in glands and hormones) at Children's Hospital diagnosed her with HPP.
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 within 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, merely 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 because they can't breathe properly. 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," Moore continued. "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. Calcium her body couldn't absorb became painful kidney stones, something to be avoided. Janelly 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 to receive an enzyme-replacement drug, called asfotase alfa, for treatment of life-threatening HPP. The medicine was developed by Enobia Pharma Corp. of Canada, which has since been acquired by Connecticut-based Alexion. Janelly had one of the most severe cases 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, at only 23 inches tall and weighing barely 19 pounds. "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." The treatment required Janelly and her parents to travel to Children's Hospital three times a week, for at least two hours each visit, to get injections of asfotase alfa. 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. After 18 months of therapy, X-rays showed visible development of her rib cage for the first time.
"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 was still almost unfathomable. But as an infant, she wasn't expected to live at all, let alone grow. "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."
Editor's note: Since this article originally published in Vanderbilt's Hope magazine in 2013, Janelly has continued to respond well to treatment. The experimental drug that regrew her bones was approved by the FDA in October 2015, and patients with all forms of childhood-onset HPP can now receive it, Simmons says. Janelly has inspired children and adults worldwide who are suffering from different forms of HPP, and her story created an awareness about the expertise and comprehensive care that pediatric and adult physicians at Vanderbilt University Medical Center and Children's Hospital are able to provide for the disorder. This post provides an update on those efforts.