Gergana Georgieva

In Romania, genetic testing for inborn errors of immunity (IEI) is recommended by pediatric, internal medicine, medical genetics, rheumatology, pediatric hematology and immunology-allergology specialists.

The (pre-test and post-test) genetic counselling is mainly performed in one of the seven National Reference Centres for Medical Genetics (see below). If the genetic testing is indicated and consented, tissue samples (usually blood) are sent to genetics laboratories from two Regional Centers of Medical Genetics (Timis and Dolj). The cost of genetic testing (clinical exome or whole exome sequencing WES) is supported from the National Program for Rare diseases. Turnaround time may vary, from (usually) 3-4 months to a year, due to limitations of funding. The counselling is fully covered by public health insurance. In urgent situations, or at the indication of the doctors, or the desire of the patients/family samples are sent to private laboratories, mainly motivated by a shorter turnaround time. The cost of genetic testing is supported by the family or sponsors (as Romanian Association of Patients with Primary Immunodeficiencies ARPID (https://arpid.ro/), Imunopedia (https://imunopedia.ro/) or other. Alongside Romanian patients with IEI, also people from Ukraine and Republic of Moldova benefited from support for genetic testing from these patient associations.

In Romania, health insurance is mandatory in order to have access to medical services in the state hospitals and clinics. Children under 18 years of age and persons during the period of education, are all covered by insurance, if they have a Romanian personal numerical code. People from Ukraine can obtain a personal numerical code and further benefit from Romanian state insurance.

There is the possibility to use research projects for funding of genetic testing. Examples include the ROGEN project 2024-2029 (https://rogen.umfcd.ro/) will incorporate WGS for a number of people with IEI.

A genetic diagnosis of IEI is usually communicated during a post-test genetic counselling to the patients or their guardians. Clinical geneticist recommends follow up by other specialists, testing in relatives (segregation analysis), and the possibility of prenatal or preimplantation genetic testing to prevent recurrence risk. IEI patients are followed up in pediatric hospitals and internal medicine hospitals.

Newborn screening for SCID and agammaglobulinemia (TREC and KREC screening) is NOT a part of obligatory screening. However, efforts are being made to introduce them.

The National Ministry of health approved three specialized expert centers (see below) for diagnostics and care of patients with IEI, however they are not a part of ERN-RITA. One center is part of ERN ReCONNET.

The National Plan for Rare diseases (updated every 2 years) prepared by the Romanian Ministry of Health for rare diseases determines the structure of the rare disease patient´s health care.

26.03.2025

Chirita-Emandi Adela, MD., PhD

Professor at Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., N°2, 300041 Timisoara, Romania.

Coordinator of the Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania.

List of expert centers for IEI approved by the Romanian Ministry of Health

Expertise center for rare diseases in the field of primary immunodeficiencies in the ” Clinical Emergency Hospital for Children Louis Ţurcanu Timişoara: Department of Allergology-Immunology (Pediatrics II section, Pediatrics III Clinic) and specialized clinic (Integrated Pediatrics Outpatient Clinic, Medical Genetics, Hematology, Oncology).
Expertise center for rare immunological and allergological diseases in the Regional Institute of Gastroenterology – Hepatology “Prof. Dr. Octavian Fodor” Cluj – Napoca through the Department of Allergology and Clinical Immunology.
Expertise center for rare autoimmune and autoinflammatory musculoskeletal diseases in the Cluj-Napoca County Emergency Clinical Hospital: Clinical Department of Rheumatology, part of ERN ReCONNET.

List of the 7 Regional Medical Genetics Centers in Romania

Bucharest Regional Center – Institute for Mother and Child Protection “Prof. Dr. Alfred Russescu” Bucharest – affiliated counties: Argeş, Buzău, Călăraşi, Giurgiu, Dâmboviţa, Ilfov, Ialomiţa, Prahova, Teleorman, Tulcea, Constanţa and Bucharest Municipality
Cluj Regional Center – Cluj-Napoca Children’s Emergency Clinical Hospital – affiliated counties: Cluj, Bistriţa-Năsăud, Sibiu, Braşov
Timiş Regional Center – “Louis Ţurcanu” Children’s Emergency Clinical Hospital Timişoara – affiliated counties: Timiş, Arad, Caraş-Severin, Hunedoara
Iaşi Regional Center – “Sf. Maria” Children’s Emergency Clinical Hospital Iaşi – affiliated counties: Iaşi, Bacău, Botoşani, Neamţ, Suceava, Vaslui, Vrancea, Galaţi, Brăila
Bihor Regional Center – Oradea County Emergency Hospital – affiliated counties: Alba, Maramureş, Satu Mare, Sălaj, Bihor
Dolj Regional Center Craiova County Emergency Clinical Hospital – affiliated counties: Dolj, Gorj, Vâlcea, Olt, Mehedinţi
Mureș Regional Center – Târgu Mureș County Emergency Clinical Hospital – affiliated counties: Mureș, Covasna and Harghita.

In the Czech Republic, genetic testing for inborn errors of immunity (IEI) is primarily conducted at specialized academic/ university hospital laboratories. The main institutions performing these tests are the Molecular Genetic Laboratory, affiliated with the Centre of Cardiovascular Surgery and Transplantation and the Medical Faculty of Masaryk University in Brno, and, to a lesser extent, the Laboratory of Molecular Genetics, Childhood Leukaemia Investigation Prague, at the University Hospital Motol in Prague. These laboratories work closely with one another, as well as with clinical immunologists and geneticists, to ensure accurate analysis and interpretation of test results.

Genetic testing for IEI is typically recommended by an immunologist, who then refers the patient to a medical geneticist. The medical geneticist is responsible for conducting genetic counselling, both pre-test and post-test, prescribing and selecting the appropriate genetic test, and evaluating the results in the context of family history. The genetic counselling process ensures that patients and their families understand the implications of genetic testing and its potential outcomes.

Genetic counselling and testing for IEI are fully covered by public health insurance (PHI) when indicated and with the patient’s informed consent. PHI is mandatory for Czech citizens, with coverage provided by the state for children and retired individuals. However, PHI only covers germline next-generation sequencing (NGS) testing once per person in a lifetime, regardless of the medical indication.
For registered refugees from Ukraine, PHI is provided by the Czech Republic. It covers full healthcare, meaning that their IEI genetic tests are also covered. However, other refugees without health insurance generally need a sponsor to undergo genetic testing.

NGS testing in the Czech Republic is conducted primarily through targeted panels and/or whole exome sequencing (WES). Recently, there has been a shift towards WES enriched with probes specific for IEI-related genes, allowing for better detection of specific IEIs sequences that might be missed by standard WES panels, such as those involving intronic or UTR sequences. This approach also facilitates a more comprehensive evaluation of CNVs in IEI-related genes. Since PHI only covers NGS testing once in a life per person, performing WES ensures that future genetic issues can be examined without requiring additional sequencing.

NGS test results are analysed and interpreted by genetic laboratories in close collaboration with immunologists and geneticists to ensure precise evaluation and clinical interpretation. Detected variants are classified based on their pathogenicity, and all findings in a patient’s case are then evaluated to determine whether they are disease-causing, disease-associated, pathogenic but not related to the patient’s phenotype, or variants of uncertain significance (VUS). Once the analysis is complete, the laboratory report is sent to the submitting geneticist and immunologist.

The median waiting time for IEI genetic test results in the Czech Republic is approximately four months, with a maximum waiting time of up to nine months. However, in cases requiring urgent testing, expedited processing is performed, with results available within two to four weeks.

Genetic testing services are available to patients from all regions, with clinical immunologists referring patients to geneticists for evaluation. Once a specific IEI diagnosis is established, patients typically receive ongoing follow-up care primarily in specialised Clinical Immunology departments at University hospitals in Prague, Brno, Hradec Králové, Olomouc, and Plzeň. Specialists in these centres can arrange functional testing available within the Czech Republic or through collaboration within ERN RITA or ESID.
Newborn screening for severe combined immunodeficiency (SCID) and agammaglobulinemia using TREC and KREC testing was implemented as a mandatory part of neonatal screening in January 2024, following the successful completion of a two-year pilot project. Two national centres, located in Prague and Brno, manage the screening process. Positive results are reported to IEI specialists at the University Hospitals in Prague and Brno. If IEI is suspected, the molecular genetic examination is then conducted.

Hana Grombirikova & Tomas Freiberger

In Slovakia, genetic testing for inborn errors of immunity (IEI) is recommended by immunologist predominantly in 3 National Reference Centres for IEI (Martin, Bratislava, Košice) and the patient is sent to medical geneticist. Medical geneticist performs genetic counselling (pre-test and post-test), prescribes and selects the test and evaluates the results in the context of clinical symptoms, family history, laboratory patterns and functional testing (if available). Tissue samples (blood, buccal swab, urine) are sent to genetics laboratories which are mostly private. The counselling and also the testing is fully covered by public health insurance (PHI) if is indicated and acquires the informed consent. PHI in Slovakia is mandatory.
MPS (massively parallel sequencing, NGS) of clinical exome (CES) or whole exome (WES) are covered by PHI by law, but it is connected with longer waiting periods for results that can reach almost the year or longer. It is possible to ask for CITO testing (in this case the result can be reached in 1 to 3 months).

There is the possibility to use research projects for funding of genetic testing. This is favourable for CES, WES testing because of quicker results. These projects are supported by the Ministry of Health of the Slovak Republic, national/international institutions, scientific societies or by biopharmaceutical companies.

A genetic diagnosis of IEI is usually communicated during a post-test genetic counselling to the patients or their guardians. Clinical geneticist recommends follow up by other specialists, testing in relatives (segregation analysis), and consults possibility of prenatal or preimplantation genetic testing to prevent recurrence risk. IEI patients are followed up in National Reference Centres for IEI.

Newborn screening for SCID and agammaglobulinemia (TREC and also KREC screening) have been started in Slovakia in January 2024 as a part of obligatory screening. Three national reference centres (Martin, Bratislava, Košice) are stated for management of recalls.

National reference centre for IEI in Bratislava is the member of European Reference Network for Rare Immunological Disorders (ERN RITA). National reference centre for IEI in Martin is further specialized for diagnostics and care of patients with Autoinflammatory disorders and Hereditary angioedema and is a part of international networks and working groups.

The National Program for Rare diseases (to the year 2030) prepared by the Commission of the Ministry of Health of the Slovak Republic for rare diseases, which includes IEI, determines the structure of the rare disease patient´s health care. The program covers centralization and prioritization of care in specialized centres for rare diseases. It includes 3 main tasks:

1. To develop public awareness of rare diseases
2. To expand the education of the professional public about rare diseases
3. To expand and improve diagnostics, treatment and care for patients with rare diseases

Adam Markocsy, MD., PhD.
Centre for Primary Immunodeficiencies, Periodic Fever Syndromes, and Hereditary Angioedema
Department of Paediatrics and Adolescent Medicine
University Hospital in Martin
Jessenius Faculty of Medicine of Comenius University in Bratislava
Slovakia