А total of about 7,000 rare diseases are known worldwide, and upon each diagnosis rests the fate of many children. When noone knows where to look for help, which medicine to give a child, where can anyone find a specialist that is engaged in researching such little-known diseases? These diseases are often inherited and should be treated in early childhood.
We discuss this in an interview with the medical doctor Professor Mathias R. Baumgartner, a specialist in rare diseases who has made significant progress in this area, chairing a joint project between the University of Zurich, the Children’s Hospital Zurich and University Hospital Zurich: radiz, the Rare Disease Initiative Zurich, aimed at the serious study and, of course, the treatment of rare diseases.
– Professor Baumgartner, what is a rare disease?
– Rare diseases are clearly defined in the European Union and in Switzerland as those with a prevalence of one case per two thousand people worldwide. However, most occur even less frequently, with a ratio of 1:100,000 or even 1:500,000, and today a total of about seven thousand of these diseases are known. They are extremely rare and most are inherited. People often become ill in their early childhood and remain disabled for their entire lives. These diseases are as yet poorly understood and, as such, possibilities for their treatment are limited.
– What else besides heredity can cause rare diseases?
– The reasons are diverse; e.g. there are rare infectious diseases. As an example of a hereditary disease, let me cite my own research. I study the process of the transformation of vitamin B12 in cells that occurs in several steps, leading to only two active cofactors essential for two enzyme proteins catalyzing vital functions in the cells. If only a single one fails, then the person becomes ill. These diseases are associated with the accumulation of specific metabolites and therefore they are called methylmalonic aciduria (Methylmalonazidurie) and homocystinuria (Homozystinurie), and sometimes they develop together. Our diagnostic laboratory serves the whole of Europe (and to an extent the whole world) in diagnosing these disorders.
The disease can also develop due to a simple nutritional lack of vitamin B12. Treatment is not difficult in these cases: the patient receives B12 and the problem is resolved. But this can be done only when the disease is diagnosed in time, and the treatment is started in time; otherwise, complications can develop. If the disease is caused by a defect in the cells, the prognosis is much more serious.
Another example is osteogenesis imperfecta, or “brittle bone disease”, which develops in mild, moderate and severe forms. It is quite common among rare diseases, there being about one case per 15,000 people. Usually, it is hereditary. Babies suffering from the severe form of osteogenesis imperfecta die before birth in the womb, or during childbirth. However, patients with mild forms of osteogenesis imperfecta can live completely normally.
– What symptoms indicate that a child is ill?
– In severe cases, the bones are already bent at birth, so when a child is born with such signs, they are often referred to us for consultation. Milder cases may result in frequent fractures without any apparent cause.
Today, we know how to manage “brittle bone disease”. It is important to start early in order to prevent complications as much as possible. Therefore, if there is even the slightest suspicion, it is necessary to consult a specialist and make a diagnosis.
– And which of the rare diseases is most prevalent? What diagnosis do you make most often?
– Cystic Fibrosis. It is associated with a metabolic disorder but also affects the lungs. The mild form of the disease does not manifest itself until adulthood, even though people are affected from birth. In Switzerland, cystic fibrosis is part of the Newborn Screening program performed at the Children’s Hospital Zurich. Early detection eliminates the diagnostic “odyssey”, reduces the number of hospitalizations and improves the odds of survival.
– How difficult is it to provide the correct diagnosis?
– Without newborn screening it can be complex. For example, thyroid hypofunction, the so-called hypothyroidism, is a congenital disease, but at first, it is ‘invisible’, and the baby looks normal. When the first symptoms appear, it may be too late to treat the disease.
Of course, there are other examples. Every child undergoes the so-called Guthrie test at birth (it has been performed in Switzerland since 1965): blood is obtained from the heels for certain markers. Analyses are performed to detect nine different rare diseases.
– For example?
– For example, phenylketonuria (PKU), another metabolic disorder. The problem is in the metabolism of amino acids. If amino acids cannot be broken down properly, the body cannot function normally. Like hypothyroidism, the disease cannot not always be detected in time without newborn screening.
Untreated, the disease leads to lesions of the central nervous system and child sufferers often grow up mentally retarded. However, with a low-protein diet to reduce phenylalanine intake and with a timely start to the treatment, you can cope with it. The child will lead a completely normal life, will grow up, will go to school… But, of course, with certain restrictions.
– And if the parents are from another country and want to perform a screening test in your laboratory for their child, what should they do?
– As a diagnostic reference laboratory we regularly receive samples from specialists from other countries. There is absolutely no need to come to us.
– Professor Baumgartner, tell us how you came to this area of research?
– In fact, my clinical interest and research area is congenital metabolic diseases. In addressing them, I gradually began to notice that there are many other similar rare diseases that do not fit the general framework. There are many problems common to them all. With whom should one talk about this? Where can one find the right specialist? How does one get help from official institutions? Which documents are needed?
And so the day came when the University of Zurich, in cooperation with the Children’s Hospital Zurich, announced the launch of the ‘radiz’ project – ‘Rare Disease Research Initiative Zurich’ – aimed at the study of rare diseases.
– What is the objective of the project?
– To combine all the available studies on this topic with the latest scientific developments and to try to arrange joint activities with other medical institutions dealing with the problem. To combine data obtained through clinical treatment of patients at the Children’s Hospital Zurich with those of adult patients treated at the University Hospital Zurich and with the research at the University. Sick children will become adults and will continue to get treatment and support from us, so we need specialists in both pediatric and adult medicine. They are rare.
– And there are so many rare diseases…
– Nobody knows the exact numbers and all calculations are approximate. In addition, I would like to improve the scope of care for such patients, which is possible. “Radiz” will combine competences in the area of rare diseases from the research and clinical practice of individual clinics in Zurich, the Children’s Hospital Zurich, the University of Zurich, and of the University Hospital Zurich.
The project consists of several initiatives. One of them is the “Helpline” hotline (www.kispi.uzh.ch/helpline-selten), a free Information Center for parents and children, accessible by phone or email for any questions about rare diseases in German. Here people are given more information: for example, where to find a medical organization or a specialist who will examine the toddler with a rare disease and offer advice, or to get support for health insurance, or to find special suggestions for treatment.
It should be understood that the parents and children that we work with are very vulnerable. They don’t have anybody they can talk to about their problems! They need a special approach.
– Who answers the phone?
– Experts specially trained for this work. They have information at hand about available help in certain cases, provided by foundations, specialists, and hospitals. We maintain an up-to-date database.
– Can patients from abroad seek your help?
– We can diagnose and treat those who come from other countries but rare diseases tend to have a chronic course, and so they will have to visit us periodically. It is impossible to get rid of the disease in a few days or weeks. The patient should be in constant communication with the doctor, and under close supervision for a long period of time.
If we talk about the primary examination, it typically takes no more than two weeks; some diagnostic test may take longer. During this time, samples are collected and analyzed. The child should not necessarily spend all their time in the hospital: he/she might well be observed as an outpatient and live together with his/her parents in a hotel.
– What should the parents do if the child suffers from a rare disease?
– No general recommendations can be provided, as every disease is different, but they should always act quickly. The main thing is to establish the correct diagnosis, and to try and find as much information as possible. These are the only possible general recommendations. I think parents know their child better than anyone and will notice if he/she feels unwell. They will be able to describe the symptoms accurately. Today, in the age of the Internet, one can find everything on the web, and even ask experts questions on a particular disease online. And also, they can seek help on the Helpline.
– How does one get a consultation with you?
– Our abilities are limited. Therefore, we look at how rare the disease is that the patient suffer from and whether it fits the profile. That is because we are specialists predominantly in only one field. For all other cases, the “Center Without Diagnosis” is being developed, which is a place to provide consultations for patients without a diagnosis.
What does a person faced with a rare disease usually do? He visits his doctor. But the doctor can not always make an accurate diagnosis because it is impossible to know all 7,000 rare diseases and the patient may show only nonspecific symptoms. Our “Center Without Diagnosis” will provide a thorough review of the patient’s history and suggest further steps.
– And if the diagnosis has already been established, can one ask you for a “second opinion”?
– Of course, if parents suspect the presence of a rare disease or the diagnosis has been established by a doctor in their country. It is best to seek information on how to obtain treatment in our clinic via the Helpline.
Mathias R. Baumgartner
Professor, Doctor of Medicine, graduated from the Medical Faculty of the University of Basel in 1992. He did his postgraduate education in experimental medicine and biology at the University of Zurich. After graduation, he worked in Basel, Paris, and Baltimore (United States). Since 2003, he has worked at the Division of Metabolism and Molecular Pediatrics at the Children’s Hospital Zurich. In 2008, he was appointed Extraordinary Professor for metabolic disorders at the University of Zurich, Head of the Division of Metabolism, as well as the Medical Director of the Neonatal Screening Program in Switzerland. Since 2012, he has headed the clinical research priority program on rare diseases at the University of Zurich, the so-called «radiz – Rare Disease Initiative Zurich», and in 2015 he became the leader of the «Competence Center for rare diseases – University Medicine in Zurich’ project within the framework of «General strategy for highly specialized medicine of the Canton of Zurich».