31 Issue 7 | 2017 | S upporting Y our P ractice HYPOPHOSPHATASIA Of Bones and Teeth What is HPP? HPP is a single-gene disorder. More than 300 mutations of the ALPL gene are responsible for HPP, with some correlation between the location of the mutation and the severity of the disease. All HPP mutations occur on the ALPL gene encoding for the enzyme TNAP (tissue-nonspecific alkaline phosphatase). “The story behind HPP is a mineralization (calcification) problem,” explains Dr. Marc McKee, professor in the faculties of dentistry and medicine at McGill University. “The bones and teeth are hypomineralized, so they’re soft and deformed.” In healthy individuals, TNAP cleaves and removes a mineralization inhibitor called PPi (pyrophosphate), a molecule that slows down mineralization to regulate carefully the way calcium-phosphate mineral crystals grow in bones and teeth. Without the enzyme, inhibitory PPi accumulates and prevents mineralization. “As a result, bone and tooth dentin don’t mineralize properly, and the acellular root cementum doesn’t form and mineralize to anchor the teeth in the jawbones via the periodontal ligament—thus the loss of teeth,” adds Dr. McKee. HPP is traditionally categorized by age of onset (perinatal, infantile, juvenile, and adult HPP), unless manifestations are limited to the teeth; in that case, it is referred to as odonto-hypophosphatasia. Prevalence While the global prevalence of HPP ranges from 1 in 100,000 to 1 in 300,00 individuals, the disease disproportionately affects certain populations. “In Manitoba, we have several unique populations where certain genetic disorders are more commonly seen than in the general population. These disorders are caused by what is called ‘founder mutations’, including HPP in our Mennonite population,” says Dr. Cheryl Rockman-Greenberg, a pediatrician and geneticist at the University of Manitoba who has been studying HPP for over 30 years. “In our Mennonite population, the prevalence of HPP is approximately 1 in 2,500 individuals.” Presentation: signs and symptoms Dentists might be the first health care providers to witness the signs and symptoms of the milder forms of HPP, as families may seek help when their child’s primary teeth exfoliate prematurely. Diagnosis “Dentists can have an enormous impact on their patients’ lives by facilitating diagnosis,” stresses Debbie Taillefer, co-founder of Soft Bones Canada, an organization that offers support to those affected by HPP and promotes research through Concerned parents bring their toddler to your clinic for help. The child has already started to lose his or her primary teeth. The exfoliation is atraumatic and caries-free, and the teeth have the roots intact. Would you be able to recognize these signs—the hallmarks of hypophosphatasia (HPP)—and know how to intervene? Primary teeth that prematurely exfoliated because of HPP. Photo courtesy of the Stimac family. X-ray of the wrist of a child with juvenile HPP demonstrating radiolucent "filling defects" at the ends of the radius and ulna with surrounding areas of demineralization and sclerosis.