Debbie Moore was 18 months old when she was diagnosed with X-linked hypophosphatemia (XLH) a rare, deforming, and painful bone disorder.
XLH causes softening of the bones (osteomalacia) and rickets. Symptoms of the disease usually surface during childhood. Patients may be short in stature with bowed legs and have bone pain or dental abscesses.
Debbie endured leg braces during much of her childhood. She also had multiple surgeries that removed bone from her tibias and femurs in an attempt to straighten her legs.
A Fifty/Fifty Chance for Colton
Debbie knew that if she had children her offspring would have a fifty/fifty chance of inheriting XLH. Her son Colton was eight years old when he began showing severe symptoms.
Even when he was born his legs were bowed, but it was not until the age of eight that he had to rely on help to lift himself up. His feet were so deformed that he had difficulty walking.
Debbie enrolled Colton in a clinical trial. The trial was based on research conducted by Dr. Michael Econs of Indiana University’s School of Medicine. Dr. Econs had been treating XLH patients since the 1980s.
About Burosumab’s Potential
Dr. Econs explains to his patients and families that in XLH the kidneys treat the phosphate in our blood as waste and eliminates it. Yet phosphate is needed for repair and growth of tissue and cells. Eighty-five percent of phosphate in our bodies is in our bones.
The trial Colton participated in investigated burosumab, a therapeutic drug that normalizes phosphate in the blood. The expectation for burosumab was to heal rickets, reduce stiffness and pain, bring the legs into better alignment, and generally promote bone healing.
A Better Life for Colton
Colton is now twelve years old and has been receiving injections of burosumab every two weeks for the last four years. Before burosumab came onto the scene, patients would receive high doses of vitamin D as well as phosphorus at various times each day.
Burosumab has made a tremendous difference in Colton’s life. He now enjoys being with his friends and even roller-skating. According to Debbie, his improvement has been extraordinary.
At some point in the future, Colton may be able to discontinue the drug.
Dr. Econ had worked with burosumab for thirty years. The drug was approved by the FDA for the treatment of children and adults on April 17, 2018.
Debbie said that although she was not able to have the benefit of a drug like burosumab for most of her life, she is thrilled that Colton and others have this opportunity because of Dr. Econ’s dedication.
About X-Linked Hypophosphatemia rickets (XLH)
XLH is a rare genetic disorder that affects one in twenty-thousand people. Although there are over fifteen alternate names for XLH, it is most commonly called X-linked hypophosphatemia rickets.
XLH develops when the mineral phosphorus is deposited into urine causing low phosphorus levels in the blood (hypophosphatemia).
Phosphorus, a mineral that builds and repairs teeth and bones, also affects muscles and supplies energy to cells. It is critical for normal development and growth.
About the PHEX Gene
Phosphopenic rickets is caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). More than five hundred mutations in the PHEX gene have been identified as a cause of XLH. The PHEX gene is responsible for making instructions for an enzyme that is found in bones and teeth.
There is evidence that the PHEX enzyme is involved in the regulation of phosphate.
XLH is Inherited
As it is an X-linked dominant disorder, people who have one PHEX gene mutation can have XLH. It is not necessary to have mutations in the PHEX gene from another parent.
If a woman has XLH there is a fifty percent chance that their children will inherit the disorder.
On the other hand, if a man has XLH, all of his daughters will inherit the condition. It will not, however, be passed along to his sons.
Not all XLH disorders are inherited. Although rare, some patients may have a random mutation, but it can still be passed along to their children.
Symptoms
Children may experience abnormal bone formation, pain, low bone density, and fractures. Other characteristics are short stature, bowed or knock-knees, abnormal gait, and weakness. Symptoms in children often appear when the child starts to stand or walk.
Adults may experience arthritis, decreased mobility, bone pain, disruption at the site of tendons and ligaments, fractures, and loss of bone density. In some cases, due to the variety of XLH symptoms, the disease may not be diagnosed until adulthood.
About the NCT03651505 Clinical Trial
Ultragenyx Pharmaceutical Inc. is currently sponsoring a clinical trial entitled: X-linked Hypophosphatemia Disease Monitoring Program. The trial investigators are collecting data on disease severity and progression in patients taking burosumab and those who are not taking burosumab.
The study will involve five hundred participants and is scheduled for completion in July 2028.
Details on this trial and the many other clinical trials investigating burosumab that are active, inactive, recruiting, or non-recruiting may be accessed by searching www.clinicaltrials.gov.
Ultragenyx is a clinical-stage biopharmaceutical company based in Novato, California that is focused on developing novel products to treat rare and ultra-rare diseases. They sell burosumab-twza under the trade name Crysvita®; it is the first and only FDA-approved therapy for the treatment of XLH.
