The story of Josie

Josie was 15 months old when we took her to see a pediatric ENT at Children’s Hospital of Philadelphia (CHOP). Josie had been a noisy breather since birth, and her pediatrician had suggested a visit with a specialist. There had been other concerns over the last year, too, including gastrointestinal and feeding issues, as well as delays in walking and crawling. Josie was receiving speech and physical therapy, and had been diagnosed with benign hydrocephalus. But it wasn’t until the Director of the Pediatric Otolaryngology Fellowship Program at CHOP assessed Josie’s narrow airway that these puzzle pieces finally began to fit together.

Recognizing the facial features typical of a rare genetic disorder known as mucopolysaccharidosis (MPS). The Doctor informed us to leave the office until he was able to expedite an appointment with CHOP’s Metabolic Disease Program. MPS-1 is a lysosomal storage disorder in which the body lacks an enzyme needed to break down sugars. These sugars build up in the body’s cells as toxic material, causing damage to the brain and other organs. The condition is progressive, so for our sweet Josie, time was of the essence.

Metabolic testing confirmed MPS-1. The disorder has a wide range of severity; Josie was diagnosed with Hurler syndrome, the most severe type. Only approximately 40 children per year are diagnosed with Hurlers in the United States. Children with Hurler syndrome can suffer from skeletal abnormalities, cognitive impairment and developmental delays, heart valve disease and respiratory problems, enlarged organs, macrocephaly, severely short stature, corneal clouding, endocrine problems and a life expectancy under 10 years of age.

Devastated, we launched into a whirlwind of tests and evaluations with specialists across CHOP, including Cardiology, Audiology, Ophthalmology, Pulmonology, Neuropsychology, Neurology, Orthopedics and Blood and Marrow Transplant. Josie was found to have an aortic leak, septal hypertrophy and a bicuspid aortic valve with stenosis; hearing loss, corneal clouding and an enlarged liver and tongue; an umbilical hernia; ventriculomegaly; low muscle tone; and several orthopedic issues, including abnormally-shaped bones, kyphoscoliosis, severe joint stiffness and hip dysplasia.

We couldn’t believe this was happening. From the outside, she looked like a happy baby with some mild delays in reaching her milestones. It was unfathomable that all of this destruction was going on inside her little body.

While there is no cure for Hurler syndrome, treatment does exist. Doctors placed a port so that Josie could receive IV enzyme replacement therapy (ERT), and they began to discuss the possibility of a bone marrow transplant. By replacing the stem cells missing the enzyme with new, healthy cells, the transplant could prompt healthy activity of the deficient enzyme.

With the potential for life-threatening complications, a bone marrow transplant was a big risk but we also felt it was Josie’s best chance. With a prognosis of rapid deterioration in her mental and physical health, coupled with a life expectancy of less than 10 years, the transplant at least gave her hope for a better quality of life.

At 18 months old, after multiple surgeries, weeks of four-hour ERT treatments and nine days of chemotherapy to prepare her body, Josie received a stem cell transplant in the Blood and Marrow Transplant Program, part of CHOP’s Cellular Therapy and Transplant Section.

Josie’s transplant was relatively uncomplicated, and we were able to return home after an extended hospital stay. Her road to recovery then began. With physical and occupational therapy, Josie stood at 22 months and began to walk at 2. She was also fitted for hearing aids and had her gastrostomy tube removed following extensive speech and feeding therapy. Shortly after her transplant, however, Josie developed graft vs. host disease, a condition in which donated cells view the recipient’s body as foreign and begin to attack it.

For Josie, the graft vs. host disease manifested on her skin, causing red, itchy lesions. Josie was put on immunosuppressants and steroids to manage the condition. Ongoing steroid use, however, can result in adrenal insufficiency. Because the body is receiving outside steroids, it stops making cortisol and becomes dependent on continued steroid use to function.

Josie was referred to the Endocrine Late Effective After Cancer Therapy (ELECT) Program — a team with expertise in identifying and treating endocrine disorders after cancer therapy, which may include chemotherapy, radiation, bone marrow transplantation or immunotherapy. Due to the length of time Josie had been exposed to outside sources of steroid, the ELECT providers, recognized she would need an extended period of time to wean off her steroids. Over a period of six months, Josie’s steroids were slowly reduced, and her body gradually began making steroid on its own again. While her adrenal issues are not yet resolved and Josie remains on immunosuppressants to help manage the graft vs. host disease, the ELECT team partners with Josie’s other specialists to closely monitor her and remains actively involved in her care.

Now 11, Josie’s condition is relatively stable. Full of spunk, she maintains her positive demeanor throughout continued therapies and medical care, which includes regular follow-ups with Endocrinology, Dermatology, Oncology, Orthopedics, Cardiology and 10 additional specialties. She will eventually need more orthopedic surgeries, and she began stress tests to monitor her heart’s function during sustained physical activity. For now, however, Josie is busy navigating elementary school and spending cherished time with her big brother, family and friends.

We greet each day with vigilance to ensure Josie gets everything she needs to live her best life. Things are constantly changing, and we have learned to be flexible with daily successes and setbacks, and to continue on with positivity and hope. There are so many things to be thankful for, and Josie is such a happy little girl. She makes us strong because she is strong. She’s our guide.