Maternal-fetal medicine and geneticist, Karin Blakemore, M.D., and prenatal genetic counselor, Chrissy Hertenstein, discuss recent research around heterozygous disease-causing alkaline phosphatase (ALPL) variants.
DOI: 10.1002/mgg3.2056 I'm Karen Blakemore, I'm the director of the prenatal diagnosis and treatment center at johns Hopkins Hospital and I'm chrissy Hartenstein, one of the prenatal genetic counselors in the prenatal diagnostic and treatment center. Our group collaborated with experts in the Greenberg Center for skeletal dysplasia at johns Hopkins dr julie hoover Fong and genetic counselor Natalie Beck to look at all individuals identified in our center by genetic carrier screening to have a pathogenic variant in the gene for hypo phosphate AsIA. HipAA phosphate asIA is an under recognized entity. It's a metabolic bone mineralization disorder that on the severe end of the spectrum can present on prenatal ultrasound with very thin fetal bones, fractures and respiratory insufficiency of birth. On the milder end, individuals might exhibit recurrent bone fractures with little to no trauma, tooth fragility or premature osteoporosis or osteopenia. Our study highlights the carriers for hipaa phosphate asIA who have just one mutation in the gene as opposed to infants who have inherited two mutations are found to have symptoms on the milder end of the spectrum that were often overlooked but had important implications for their health carrier screening for pregnant persons and couples is now available for hundreds of recessive diseases that might affect a child for disorders like cystic fibrosis, sickle cell, spinal muscular atrophy and many others. Today. The larger carrier screening panels include the gene for hyper phosphate asia. People with just a single pathogenic mutation in the gene for hyper phosphate asia who are carriers, in other words, may actually manifest with the symptoms that dr Blakemore mentioned. Sometimes we have picked up carriers in an unborn fetus by ultrasound, where we see just mild bowing of one bone. And in asking the parents, we find that one of them has a history of teeth or bone fragility or bone and joint pain that may go along with osteoporosis. We then did a study asking patients who are found to be a carrier for the gene for hyper phosphate asia. If they had experienced these kinds of symptoms. Together with the Greenberg Center, we developed a multidisciplinary referral and evaluation protocol for our carriers of this gene. All who agreed to be evaluated were found to have manifestations of hypothesis. Fantasia, this condition has many forms appropriate attention to carriers for hipaa phosphate asIA allows patients to receive accurate information for not only the reproductive risk, but also for their own future health. The importance of knowing about carrier status for the hyper phosphate. Asia jean extends from the unborn fetus to Children to adults of all ages. It has particular implications for adults, because so many patients diagnosed with osteoporosis are often prescribed bisphosphonates, but adults whose osteoporosis is actually secondary to hyper phosphate. AsIA should not take bisphosphonates. These medications can actually worsen the disease process increasing the risk for fractures. We hope that our findings will alert medical professionals across the country and around the world to the implications of finding a mutation in the gene for hyper phosphate asia and assure that appropriate medical management be afforded to them