Assoc. Prof. Avdzhieva, what diseases do you diagnose and treat at your clinic?
The Genetics Clinic is the only clinic of its kind in Bulgaria. Children from all over the country who are affected by any of the diseases that fall within three big groups: inborn errors of metabolism; malformation syndromes; and chromosomal disorders are admitted to our clinic. When we find the accurate diagnosis, this is good news no matter how scary this diagnosis sounds. Regrettably, for the majority of rare diseases there is no cure. We are able to treat merely twenty diseases or so, while there are thousands of rare diseases out there.
Are you the only medical institution that can diagnose these genetic disorders?
These diseases can be diagnosed at any university hospital that has suitably qualified medical specialists. However, only in our hospital there is a dedicated unit with specialists who work exclusively with this kind of pathology.
Are doctors in Bulgaria knowledgeable about rare diseases?
In addition to being clinicians my colleagues and I also teach at the Department of Pediatrics of the Medical University in Sofia. The curable lysosomal storage diseases we are discussing here are included in the curriculum. This means that the students, trainee doctors, and residents who train at our hospital, including the colleagues taking the postgraduate training courses are familiar with these diseases. Besides, there are always presentations on this topic at all pediatric conferences that are held in Bulgaria, which are quite numerous by the way and which are visited mostly by pediatricians and general practitioners. Moreover, we hold targeted meetings with our colleagues, experts in other fields of medicine, who are very likely to meet patients with those diseases.
How, for example, a child with Gaucher disease can reach your clinic?
It’s usually difficult for children with Gaucher disease to find their way to us. The problem with diagnosing rare diseases is that doctors rarely think about them. Of course, it very much depends on the specific disorder. In the case of Gaucher disease, for example, these children most commonly get referred either to oncohematologists because they have anemia and low platelet count that causes bleeding, or to pediatric gastroenterologists because the liver and spleen are enlarged. If our colleagues manage to reach the correct diagnosis, they send them to us because our clinic is the center where children with Gaucher disease receive treatment by enzyme replacement therapy.
How is the diagnosis confirmed?
The disease is caused by an inherited deficiency of a single specific enzyme. This leads to accumulation in the body of the substance that would normally break down this enzyme. Gaucher disease is in fact diagnosed by measuring this enzyme activity in a blood sample. The test is done at the National Genetic Laboratory at Maichin Dom Specialized Obstetrics and Gynecology Hospital; it is included in a clinical pathway and is paid for by the National Health Insurance Fund. Therefore, in a case where a doctor considers Gaucher disease a likely diagnosis, there is no problem to get this diagnosis confirmed in Bulgaria. It’s advisable to perform genetic testing as well. Finding the mutations is very helpful for prenatal diagnostics in case of subsequent pregnancy in the family. Gaucher disease is an autosomal recessive disorder which means that with each subsequent pregnancy there is a significant risk (25%) of giving birth to a child affected by the disease.
What happens to people who are misdiagnosed?
Gaucher disease is a progressive disease, which causes gradual damage to the liver, the spleen and the bones. The damage to the skeleton leads to severe osteoporosis, massive cerebral infarction and bone tissue necrosis. As a result, the patients can become disabled. If the diagnosis is delayed and the disease has progressed too much, the damaged bones cannot be restored. Therefore, therapy should start before any irreversible damage has occurred. And that’s why early diagnosis is in the focus of our efforts. Only then the therapy can be used effectively.
Are newborns screened for Gaucher disease?
No. Only one of the diseases we work with, phenylketonuria, is included in the national-level neonatal screening. None of the curable lysosomal storage diseases are included in this screening program.
How much time does it take to diagnose Gaucher disease, on the average?
In a publication of colleagues abroad it is reported that diagnostic delay for 1 out of 6 patients is greater than 7 years. There is no such statistics for Bulgaria. We have a patient who was diagnosed when she was in her seventies. Of course, the severity of the disease matters, i.e., how noticeable the symptoms are in the individual patient.
Is the therapy for Gaucher disease accessible to patients?
Yes, this therapy is fully covered by the National Health Insurance Fund both for adults and children alike. The sustained effort over many years of doctors and patient organization made this possible. Now a patient can start treatment right after being diagnosed. The therapy is really very effective; it reverses symptoms in just a few months.
Could you please explain a bit more about Hunter syndrome. Does it have any specific symptoms or not, which could lead to misdiagnosis?
The earliest symptoms start as early as the first year of the child. They include frequent respiratory tract infections, umbilical and inguinal hernias. These are not specific symptoms and often at this early stage of the disease the diagnosis is missed. Afterwards, during the second or third year, depending on the severity of the disease, the infant can manifest specific symptoms: gradual thickening of the facial features, enlargement of the head, occurrence of joint contractures (the range of motion of the joints is impaired and it is difficult for the infant to grasp objects). So, the combination of coarse facial features, a larger head and joint contractures are very characteristic of Hunter syndrome and the rest of the mucopolysaccharidoses. It is not difficult to diagnose such patients even solely on the basis of their physical appearance. These children also have enlarged liver and spleen, which means that their belly is bigger than normal, and the heart is also affected. Some of the patients show neuropsychological regression; seizures may also occur. But those symptoms are present at a more advanced stage of the disease.
Is there a cure available for Hunter syndrome?
Just like with Gaucher disease, with Hunter syndrome the body is missing a single specific enzyme and the patients receive enzyme replacement therapy. The drug is administered intravenously, once a week. The therapy is fully covered by the National Health Insurance Fund. Right after the diagnosis is established, the patient can start treatment. Thanks to the enzyme replacement therapy the size of the liver and the spleen decreases, the heart stabilizes and joints mobility improves. The limitation of this therapy is that it cannot reach the brain and does not have any effect on the neurological damage in those children. The good news is that a lot of effort is currently dedicated to this field. New therapies that have the potential to solve this problem are being developed. Some of them are in the last phase of clinical research.
The enzyme replacement therapy helps us improve the quality of life and extend the life span of patients with Hunter syndrome, and keep their condition stable until those new and more effective therapies obtain marketing authorization.