First Treatment Protocol for PAPP-A2 Deficiency Emerging

Published December 1, 2017 | Journal of Clinical Endocrinology and Metabolism

In 2015, researchers at Cincinnati Children’s discovered two genetic mutations responsible for a novel growth disorder called PAPP-A2 deficiency. Just a few months later, they turned their attention to developing a treatment protocol for a clinical trial. Now, results from the first year of the experimental therapy are in.

PAPP-A2 deficiency results in higher circulating levels of total insulin-like growth factor 1 (IGF-1) but low levels of free insulin-like growth factor 1 (fIGF-1), and is characterized by short stature, insulin resistance and below-average bone mineral density.

So far, only five people in the world have been diagnosed with PAPP-A2 deficiency: three siblings in New York and two siblings in Spain. Two of the New York siblings received drug therapy through the Cincinnati Children’s study.

The experimental treatment used standard dosages of recombinant human insulin-like growth factor 1 (rhIGF-1), which is typically used to treat another IGF-1 deficiency disorder called Laron Syndrome.

One sibling discontinued treatment after developing pseudo-tumor cerebri, a known side effect of rhIGF-1. But the other experienced an increase in height velocity, resolution of insulin resistance and an increase in total-body bone mineral density.

Based on a patient’s blood work, PAPP-A2 deficiency could easily be misdiagnosed as idiopathic, says Catalina Cabrera-Salcedo, MD, the study’s first author. She adds it is likely that many people have the condition and are not aware of it.

“A few years ago, we didn’t know the genetic mutation existed, so it is exciting to see even modest results from this treatment protocol,” says Cabrera-Salcedo, a third-year endocrinology fellow at Cincinnati Children’s. “The patient is continuing therapy, and we will follow the progress closely.”