The Chair of Pediatrics and Adolescent Medicine at the Johannes Kepler University Linz’ Faculty of Medicine is thereby turning the JKU into a leading world center to study this rare disorder

Hypophosphatasia (HPP) is a non-curable, hereditary bone metabolism disorder in which the bones’ low mineral content can lead to severe skeletal malformation. Patients can suffer from rickets, bone fractures, muscle weakness, fatigue, rheumatic pain, and/or the early loss of baby teeth, including the teeth roots. One in 100,000 children is diagnosed with a severe form of HPP. JKU Prof. Wolfgang Högler, head of the University Department of Pediatrics and Adolescent Medicine at Kepler University Hospital, remarks: "We believe, however, that it affects many more people. While we are aware of the severe cases, some adolescents and adults experience milder forms and some are currently difficult to diagnose." The frequency of moderate or mild forms is assumed to be 1 in 7,000.

The more severe the disorder, the earlier it occurs and the earlier it can be diagnosed. In very severe cases, at birth the bones are barely visible on x-rays. The milder form does not usually begin until puberty and often goes unnoticed.

Quicker Diagnosis
Prof. Högler's study focuses on the milder forms. Prof. Högler added: "Findings from the Global HPP Registry Study show that in many cases, diagnosing HPP can be delayed by years. By this time, patients often have a long odyssey behind them before their disorder is even properly diagnosed."

As mutations in the ALPL gene cause the disorder, the patient diagnosis requires a blood test, an x-ray, and a gene test. The problem is that there are a large number of ALPL gene mutations. Prof. Högler explains, "As there are a number of mutations for this particular gene, it is difficult to determine whether the HPP disorder is present or not." His research group is currently studying these gene mutations which are now being sent from all over the world to Linz for testing. Using special lab techniques, the mutations are introduced into a human cell line. Cell cultures can then be used to show just how much the modified cell has mineralized and how faulty the cell function is. In other words, the genetic mutations are tested in the lab in cell cultures to determine their disorder value - i.e. their mineralization capacity. The findings are reviewed by a global consortium of scientists led by Prof. Högler and subsequently processed in a public database.

Global Database on the JKU Homepage
Prof. Högler added, "A global, publicly accessible website will be set up on the JKU homepage that will provide information about all of the ALPL gene mutations we – and other researchers - have discovered. This database will serve as a reference tool for physicians and geneticists who treat or counsel patients who have this disorder." The seven-member team will obtain, triage, test and publish the genetic mutation codes from around the world. The researchers will not provide any biological material for this purpose, only the code to be tested. All of the information ranging from cell function to correlating patient symptoms will be entered into the reference guide. Classifying as many gene mutations as possible will make diagnosing HPP much easier in the future.

€ 1.4 Million in Funding
Developed by Prof. Högler and laboratory manager Dr. El-Gazzar, the study will receive € 1.4 million in funding provided by Alexion, a biopharmaceutical company that specializes in rare disorders. The research findings are expected to provide a better understanding of the disorder. "Network-based research is essential for scientific knowledge gain. There is no doubt that this study will make the JKU a hub and globally recognized center of activity for this particular disorder," said Prof. Högler.

JKU Rector Meinhard Lukas remarked: "Since its inception, one of the JKU Faculty of Medicine’s guiding principles is to create medicine that can directly serve the people. Prof. Högler's research is once again filled with life. We are proud that the JKU and its fairly new Faculty of Medicine is becoming a global research center for this serious disorder and this continues to drive us forward. It demonstrates just how great the trust in both our researchers’ expertise and in our university is. I congratulate Prof. Högler warmly and wish him every success."

Elgin Drda, Vice-Rector and Dean of the JKU Faculty of Medicine added, "Prof. Högler’s ambitious study means that the Faculty of Medicine is not only taking a global lead in an important study, but also assuming social responsibility. When it comes to rare disorders, it is often difficult to provide sufficient human resources and funding to support research. Being able to quickly provide a clear diagnosis of the disorder will not only greatly improve the children’s quality of life, but the parents as well."