Hypophosphatemia and the Secret Locked in a Child’s DNA

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A toddler is taken to his pediatrician because his parents are concerned he might be small for his age. The pediatrician diagnoses him with knock knees, but there’s no cause for alarm.

Although the child doesn't have any other known medical conditions, something is happening in secret, inside his DNA that won’t be discovered until a diagnosis of hypophosphatemia is discovered some time later. And if this disease is ignored, it can quickly become deadly.

But back to that first appointment. “At that time, he had a rather normal diet, was taking [multivitamins] so his intake of vitamin D was at the recommended daily allowance,” shares Dr. Michael Levine, a pediatric endocrinologist at the Children's Hospital of Philadelphia. “And because he had no other medical disorders and no other conditions that were of concern, his pediatrician decided that they would just watch him to see whether he could outgrow his knock knees, and whether this might improve his overall growth.”

At the age of 7, there is little to no progress. He visits an endocrinologist. Nothing significant is found. At 10, an orthopedic surgeon operates on the child’s knock knees.

Two years later, he visits Dr. Levine for the first time. “When we first saw him, we were impressed by his prior history of knock knees, which had its onset in his toddler years, and we looked carefully at the evaluation that his pediatric endocrinologist had performed some years prior that disclosed normal levels of serum calcium, normal levels of PTH, normal alkaline phosphatase, and a normal serum 25-hydroxy vitamin D, which in the mind of the first pediatric endocrinologist had effectively ruled out rickets or osteomalacia.”

But one test hadn’t been done — a test for serum phosphorus level, and when the results come back showing hypophosphatemia, this becomes a key to the child’s diagnosis.

“When you have a child that doesn't respond as you might expect to calcium and vitamin D,” advises Dr. Levine, “you have to take that next step and begin to ask, could this be due to a genetic defect in the vitamin D system, or could it be a genetic defect in phosphate metabolism?”

As it turned out, the child’s disease was genetic, and this unlocked the path to treatment. And while everything worked out in the end, it’s hard not to think about how this story could have been very different had one simple test been run, or if genetics had been considered sooner.