The Toddler Was Bowlegged, Her Gait Awkward. What Was It?

Paloian and Nemeth had reviewed the X-ray and labs. Like Furukawa, they weren’t sure exactly what was causing the little girl to lose so much phosphate that her bones were bending. From talking to the parents, it was clear that it wasn’t a problem of nutrition. And while there are other diseases that can cause this kind of phosphate wasting, children with those disorders usually look sick. This child, though small and bowlegged, looked quite healthy, and her exam was otherwise normal. They would need to get more tests, Paloian explained to the anxious parents. This could be an inherited disease known as X-linked hypophosphatemia. It was a rare disease, but they saw a lot of it in their specialty clinic. In order to prove that that’s what their daughter had, she would need genetic testing. And no matter what she had, it was essential that they get her phosphate levels as close to normal as possible. To do that, the child would have to take packets of phosphate three or four times a day. It tasted pretty bad, the doctor conceded, but it was the only way to strengthen her bones.

X-linked hypophosphatemia, as the name suggests, is a disease that is inherited on the X chromosome. In this disorder, there’s an error in the chromosome, which causes the kidneys to dump phosphate in the urine. Normally for a patient to have this, she would have to inherit it from one of her parents. Yet neither of this girl’s parents had any history of a bone problem. The abnormality can arise from a spontaneous mutation, but that is extremely rare. The genetic test came back positive; the child had X-linked hypophosphatemia. Her parents were tested as well. Neither of them had it. The girl was the first in her family but may not be the last. Her children, should she choose to have them, would have a 50-50 chance of inheriting this abnormal gene.

Treatment was not easy. The supplemental phosphate tasted awful. And she had to take it several times a day. Every day. The blood levels of the essential mineral began to rise, but her legs stayed bowed. That was the best you could do with this treatment. Replacing the missing mineral was enough to slow the disease but not to reverse the damage.

Two years after this child got her diagnosis, the Food and Drug Administration approved an orphan drug designed specifically for this disorder, called burosumab. Taken twice a month, the medication increases serum phosphate levels by reducing the amount lost through the kidneys.

Like so many of these new biopharmaceuticals, burosumab is expensive — roughly $150,000 a year. Lucky for her, her parents’ insurance was willing to pay for most of it. The drug has been amazing. She is 6 now, and though she remains one of the smallest in her class, her legs look normal to all but the most expert eye. Even more important: She can run and jump and have an active life. Her newest passion is gymnastics.

Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmd

Source link