"It’s a thread that has been running through my life throughout my medical career," said McCabe about AHC, a rare and often fatal condition which is carried by females but manifested in male children. "We identified two boys who had this disease no one had ever seen before. We pursued answers biochemically for about a decade, and ultimately cloned genes associated with the condition."

According to McCabe, this research demonstrates the rapid translation of molecular genetic information from the basic science lab to the patient. "Within two weeks of cloning the gene, we had a call from a colleague. She was counseling a pregnant woman whose nephews had died of AHC. The woman was considering terminating her pregnancy."

McCabe’s lab received sample cells from the woman and from her amniocentesis. "We took a DNA probe, and using a test called fluorescence in situ hybridization (FISH), we were able to determine that the woman’s child was not at risk because she was not a carrier."

AHC, which affects one in 10,000 children, is caused by a mutation of a gene on the X-chromosome. It causes abnormal development of the adrenal gland, which in turn interferes with the body’s ability to adapt to stresses associated with even mild illness. If diagnosed early, affected children can be treated with steroids. Often, however, AHC patients die before diagnosis can be made.

McCabe is continuing with clinical studies of the disease. "We’re attempting to understand how this gene regulates the development of the adrenal gland, " he said. "We’ve also learned that the gene is expressed not only in the adrenal cortex, but also in the brain, so these boys don’t go through puberty normally. I’m currently doing very basic investigations, actually looking into the development of the human organism, to put all the pieces together."

According to McCabe, "It was our concern for our patients that started us on this path. It is very gratifying to apply our work directly to affected patients. And I hope in the future we will be able to do still more for their benefit."