. 2022 Mar 24;17(1):136.

doi: 10.1186/s13023-022-02285-x.

The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers

Anna Tylki-Szymańska¹, Zsuzsanna Almássy², Violetta Christophidou-Anastasiadou³, Daniela Avdjieva-Tzavella⁴, Ingeborg Barisic⁵, Rimante Cerkauskiene⁶, Goran Cuturilo^{7

8}, Maja Djiordjevic⁹, Zoran Gucev¹⁰, Anna Hlavata¹¹, Beata Kieć-Wilk¹², Martin Magner^{13

14}, Ivan Pecin¹⁵, Vasilica Plaiasu¹⁶, Mira Samardzic¹⁷, Dimitrios Zafeiriou¹⁸, Ioannis Zaganas¹⁹, Christina Lampe²⁰

Affiliations

¹ Department of Pediatric Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
² Department of Toxicology and Metabolic Diseases, Heim Pal Children's Hospital Budapest, Budapest, Hungary.
³ Archbishop Makarios III Hospital, Nicosia, Cyprus.
⁴ Department of Clinical Genetics, University Pediatric Hospital, Sofia, Bulgaria.
⁵ Centre of Excellence for Reproductive and Regenerative Medicine, Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia.
⁶ Clinic of Paediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
⁷ Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁸ University Children's Hospital, Belgrade, Serbia.
⁹ Mother and Child Health Care Institute of Serbia, Medical University of Belgrade, Belgrade, Serbia.
¹⁰ University Children's Hospital, Skopje, North Macedonia.
¹¹ National Institute of Children's Diseases, Department of Paediatrics, Medical Faculty Comenius University, Centre for Inherited Metabolic Disorders, Bratislava, Slovakia.
¹² Unit of Rare Metabolic Diseases, Department of Metabolic Diseases, Jagiellonian University Medical College, University Hospital, Krakow, Poland.
¹³ Department of Paediatrics, University Thomayer Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁴ Department of Pediatrics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁵ University Hospital Centre Zagreb, Department of Internal Medicine, Division of Metabolic Diseases, Zagreb School of Medicine, Zagreb, Croatia.
¹⁶ Regional Centre of Medical Genetics, INSMC Alessandrescu-Rusescu, Bucharest, Romania.
¹⁷ Institute for Sick Children, Department of Pediatric Endocrinology and Metabolism, Medical School, University of Montenegro, Podgorica, Montenegro.
¹⁸ First Department of Pediatrics, Hippokratio General Hospital, Aristotle University, Thessaloniki, Greece.
¹⁹ Neurogenetics Laboratory, Neurology Department, University Hospital of Heraklion, University of Crete, Heraklion, Greece.
²⁰ Department of Child Neurology, Epileptology and Social Pediatrics, Centre for Rare Diseases, University of Giessen, Standort Giessen, Feulgenstr. 12, 35389, Giessen, Germany. christina.lampe@paediat.med.uni-giessen.de.

PMID: 35331284
PMCID: PMC8943501
DOI: 10.1186/s13023-022-02285-x

The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers

Anna Tylki-Szymańska et al. Orphanet J Rare Dis. 2022.

. 2022 Mar 24;17(1):136.

doi: 10.1186/s13023-022-02285-x.

Authors

Affiliations

¹ Department of Pediatric Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
² Department of Toxicology and Metabolic Diseases, Heim Pal Children's Hospital Budapest, Budapest, Hungary.
³ Archbishop Makarios III Hospital, Nicosia, Cyprus.
⁴ Department of Clinical Genetics, University Pediatric Hospital, Sofia, Bulgaria.
⁵ Centre of Excellence for Reproductive and Regenerative Medicine, Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia.
⁶ Clinic of Paediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
⁷ Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁸ University Children's Hospital, Belgrade, Serbia.
⁹ Mother and Child Health Care Institute of Serbia, Medical University of Belgrade, Belgrade, Serbia.
¹⁰ University Children's Hospital, Skopje, North Macedonia.
¹¹ National Institute of Children's Diseases, Department of Paediatrics, Medical Faculty Comenius University, Centre for Inherited Metabolic Disorders, Bratislava, Slovakia.
¹² Unit of Rare Metabolic Diseases, Department of Metabolic Diseases, Jagiellonian University Medical College, University Hospital, Krakow, Poland.
¹³ Department of Paediatrics, University Thomayer Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁴ Department of Pediatrics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁵ University Hospital Centre Zagreb, Department of Internal Medicine, Division of Metabolic Diseases, Zagreb School of Medicine, Zagreb, Croatia.
¹⁶ Regional Centre of Medical Genetics, INSMC Alessandrescu-Rusescu, Bucharest, Romania.
¹⁷ Institute for Sick Children, Department of Pediatric Endocrinology and Metabolism, Medical School, University of Montenegro, Podgorica, Montenegro.
¹⁸ First Department of Pediatrics, Hippokratio General Hospital, Aristotle University, Thessaloniki, Greece.
¹⁹ Neurogenetics Laboratory, Neurology Department, University Hospital of Heraklion, University of Crete, Heraklion, Greece.
²⁰ Department of Child Neurology, Epileptology and Social Pediatrics, Centre for Rare Diseases, University of Giessen, Standort Giessen, Feulgenstr. 12, 35389, Giessen, Germany. christina.lampe@paediat.med.uni-giessen.de.

PMID: 35331284
PMCID: PMC8943501
DOI: 10.1186/s13023-022-02285-x

Abstract

Background: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the picture of disease management in the region and understand ERT implementation. Since the considerable number of MPS IVA patients in the region, particularly adults, the study mainly focused on MPS IVA management and treatment.

Results: 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding.

Conclusions: The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions, regarding epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.

Keywords: Enzyme replacement therapy; Morquio A syndrome; Mucopolysaccharidoses; Southern and Eastern European countries; Treatment accessibility.

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Conflict of interest statement

Z. Almassyzs, V. Christophidou-Anastasiadou, I. Barisic, R. Čerkauskienė, M Djordjevic, A. Hlavata, B. Kiec-Wilk, V. Plaiasu, M. Samardzic have no competing interests to declare. D. Avdjieva-Tzavella has received speaker honoraria, travel and accommodation funding from Takeda and Sanofi Genzyme. G. Cuturilo has received speaker honoraria and/or travel grants from BioMarin, Takeda and Sanofi Genzyme. Z. Gucev has received speaker and advisory board honoraria from Novo Nordisk, Merck, and Takeda. C. Lampe has received advisory board and speaker honoraria, travel expenses and consultancy honoraria from Sanofi, BioMarin, Amicus, Alexion, Takeda, Chiesi, Regenxbio. M. Magner has received speaker honoraria from BioMarin and Takeda and consultancy fees from BioMarin and Chiesi. I. Pecin has received advisory board and speaker honoraria from Sanofi, Sandoz, Genzyme, Takeda, Amicus. A. Tylki-Sziymanska has received speaker honoraria and/or travel grants from BioMarin, Sanofi Genzyme, Alexion, Chiesi, and Shire/Takeda. D. Zafeiriou has received honoraria, travel and research grants from Sanofi-Genzyme, Takeda, BioMarin, Novartis, Biogen and UCB. I. Zaganas has received consultancy honoraria from Akcea, Alnylam, BioMarin, Genesis Pharma, Roche, Specifar/Teva.

Figures

**Fig. 1**
South and Eastern European countries involved in the “Mucopolysaccharidosis Management Physician Survey”, in yellow

**Fig. 2**
Physicians’ main specialty as reported after the first survey. In parentheses the absolute number of specialists

**Fig. 3**
Relative frequency (%) of MPS types in the population of patients from all centers

**Fig. 4**
Relative frequency (%) of MPS types in the population of ERT treated patients

**Fig. 5**
Appropriate methods to confirm diagnosis of MPS IVA before starting ERT treatment (% of respondents).

**Fig. 6**
Respiratory function parameters considered appropriate to demonstrate the clinical benefit of ERT in patients with MPS IVA (% of respondents)

**Fig. 7**
Cardiac function parameters considered appropriate to demonstrate the clinical benefit of ERT in patients with MPS IVA (% of respondents)

See this image and copyright information in PMC

References

1. Muenzer J. Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 2011;50(Suppl 5):v4–12. - PubMed
1. Zhou J, Lin J, Leung WT, Wang L. A basic understanding of mucopolysaccharidosis: incidence, clinical features, diagnosis, and management. Intractable Rare Dis Res. 2020;9(1):1–9. - PMC - PubMed
1. McBride KL, Flanigan KM. Update in the Mucopolysaccharidoses. Semin Pediatr Neurol. 2021;37:100874. - PubMed
1. Hobbs JR, Hugh-Jones K, Barrett AJ, Byrom N, Chambers D, Henry K, et al. Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet. 1981;2(8249):709–712. - PubMed
1. Lampe C, McNelly B, Gevorkian AK, Hendriksz CJ, Lobzhanidze TV, Pérez-López J, et al. Transition of patients with mucopolysaccharidosis from paediatric to adult care. Mol Genet Metab Rep. 2019;21:100508. - PMC - PubMed

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The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers

Affiliations

The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources