February 28 is Rare Disease Day. Rare does not mean just low in number: approximately 7% of the population are affected by the 7,000 rare diseases known at present, meaning that throughout Europe, some 30 million people are affected. Researchers and physicians at the Johannes Kepler University and the Kepler University Hospital are currently conducting ground-breaking research to treat these types of diseases.

The Department of Pediatrics and Adolescent Medicine was established in 2018 at the Kepler University Hospital and department head Prof. Wolfgang Högler’s activities include conducting research and treating rare diseases.

Patients affected by rare diseases experience an enormous amount of psychological stress and strain, not only during the period leading up to the diagnosis, but afterwards as well. In addition, the more unusual and rarer a disease is, the more expensive treatment can be and spending several hundreds and thousands of euros annually per patient is not uncommon. Leading hospitals in Europe and in the EU itself have long understood that patients suffering from a rare disease can really only be treated at specialized centers where there is a higher level of expertise, healthcare professionals with years of extensive training and education in that particular field, as well as active involvement in globally networked research projects.

Professor Högler spent 13 years at leading endocrinology institutions in English-speaking countries before accepting his appointment to Linz and remarked: "Thanks to advanced technologies in DNA/RNA sequencing, diagnostics have improved greatly. When it comes to complex cases, our research network and my research laboratory at the JKU’s new Faculty of Medicine campus gives us opportunities to dive even further into the genetical material to look for causes or track down the disease mechanisms. This kind of research has paved the way to developing many new types of treatment; there are wonderful examples of enzyme replacement therapies and, more recently, gene therapy, all of which are experiencing success on a revolutionary scale."

Experts in Prof. Högler’s team in Linz are part of internationally active networks that aim to give as many patients as possible access to studies as well as new treatment options. As part of the European Reference Network for Rare Diseases, doctors and nurses work in specialized teams. One example of a rare disease is hypophosphatasia (HPP), a hereditary, incurable bone metabolism disorder in which the bones lack sufficient mineral content, leading to severe skeletal malformations. Patients suffer from rickets, bone fractures, muscle weakness, fatigue, rheumatic pain, and the early loss of baby teeth, including the root. Approximately 1 in 7,000 experience a moderate or mild form of HPP. The more severe the disease, the earlier it tends to manifest and the earlier it can be diagnosed. Diagnosing HPP includes a blood test and an X-ray, however, genetic testing is crucial as the disease is caused by mutations in the ALPL gene. The problem is that the ALPL gene has a large number of variants and the extent of the disease can sometimes be unclear. This is where Prof. Högler’s research comes in. The JKU website features a global, publicly accessible site that lists all of the known ALPL gene variants. This particular database serves as a reference for experts from around the world who are involved in treating this disease. The project team in Linz receives the genetic codes for ALPL variants from around the world, conducts cell-culture testing to determine disease value, and presents the findings to an international group of experts led by Prof. Högler. The database includes all of the information published about the gene variant’s disease value to date, ranging from cell function to the patients’ corresponding symptoms. By classifying as many gene variants as possible, the idea is to facilitate diagnosing HPP in the future. The project was created by Prof. Högler and laboratory manager Dr. El-Gazzar with funding in the amount of € 1.4 million provided by a biopharmaceutical company, Alexion, which specializes in rare diseases. The research findings are expected to provide a better understanding of the disease. Prof. Högler added, "Network-based research is essential in an effort to learn more and acquire a greater understanding."

Pediatrics and Adolescent Medicine in Transition

Tremendous advances in diagnostic tools are transforming pediatrics and medical education at the Kepler University Hospital, a place where congenital diseases and metabolic disorders are initially diagnosed and treated. As there are approximately 7,000 rare diseases, creating a central hub as well as specializing in a field are an absolute must in the area of pediatrics; the large number of special outpatient clinics are a testament to the core idea. One example of rapid developments in medical care on a university level is epilepsy. Two decades ago, there was little aetiological research in this area and patients simply accepted the diagnosis of epilepsy, focusing more on being seizure-free but without understanding why he/she had the disease. In 2022, diagnosing "epilepsy" has evolved into more than 130 specific clinical pictures, mostly of genetic origin, and each with a specific disease mechanism. The same applies to dwarfism, bone brittleness, and many types of hormonal disorders. Prof. Högler pointed out the challenges and future opportunities: "It goes without saying that each of these individual diseases also require tailored treatment plans, and our clinical research within international networks is quite pivotal in order to create and provide individual treatment."

Prof. Högler added: "As researchers, we have to turn our attention to what was once previously considered inexplicable and also teach these subjects because today's research are tomorrow’s cures."

Main Focus at the University Hospital on Pediatrics and Adolescent Medicine

The Department of Pediatrics and Adolescent Medicine has extensive expertise in the areas of endocrinology (hormones), osteology (bones), and neurology (nervous system and muscles), hereby providing the medical care not only required in this region, but also beyond state borders.

Research and disease management care focuses on insufficiency and hormonal disorders pertaining to adrenal glands, gonads, the pituitary gland, the thyroid gland, and the parathyroid gland.

• Growth and puberty disorders
• Rickets, bone brittleness; rickets
• Type 1-3 diabetes
• Therapy-resistant forms of epilepsy
• Neuromuscular diseases and movement disorders
• Oncology and hematology