Consensus statement on enzyme replacement therapy for mucopolysaccharidosis IVA in Central and South-Eastern European countries

Martin Magner; Zsuzsanna Almássy; Zoran Gucev; Beata Kieć-Wilk; Vasilica Plaiasu; Anna Tylki-Szymańska; Dimitrios Zafeiriou; Ioannis Zaganas; Christina Lampe

doi:10.1186/s13023-022-02332-7

Consensus statement on enzyme replacement therapy for mucopolysaccharidosis IVA in Central and South-Eastern European countries

Orphanet J Rare Dis. 2022 May 10;17(1):190. doi: 10.1186/s13023-022-02332-7.

Authors

Martin Magner¹, Zsuzsanna Almássy², Zoran Gucev³, Beata Kieć-Wilk⁴, Vasilica Plaiasu⁵, Anna Tylki-Szymańska⁶, Dimitrios Zafeiriou⁷, Ioannis Zaganas⁸, Christina Lampe⁹

Affiliations

¹ Department of Paediatrics and Inherited Metabolic Disorders, General University Hospital and First Faculty of Medicine, Charles University, KPDPM 1. LF UK a VFN v Praze, Ke Karlovu 2, 128 08, Prague, Czech Republic. martin.magner@vfn.cz.
² Department of Toxicology and Metabolic Diseases, Heim Pal National Pediatric Institute, Budapest, Hungary.
³ University Children's Hospital, Skopje, North Macedonia.
⁴ Unit of Rare Metabolic Diseases, Department of Metabolic Diseases, Jagiellonian University Medical College, University Hospital, Krakow, Poland.
⁵ Regional Centre of Medical Genetics, INSMC Alessandrescu-Rusescu, Bucharest, Romania.
⁶ Department of Pediatric Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
⁷ First Department of Pediatrics, Hippokratio General Hospital, Aristotle University, Thessaloniki, Greece.
⁸ Neurogenetics Laboratory, Neurology Department, University Hospital of Heraklion, University of Crete, Heraklion, Greece.
⁹ Department of Child Neurology, Epileptology and Social Pediatrics, Centre for Rare Diseases, University of Giessen, Giessen, Germany.

Abstract

Background: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. A progressive systemic skeletal chondrodysplasia, leading to significant morbidity and reduced life expectancy is the main clinical feature of this multisystemic disease. Although enzyme replacement therapy with elosulfase alfa is established in Europe, the rarity of disease and other factors still set hurdles in having patients treated in some countries. Aim of this statement is to provide evidence-based guidance for the enzyme replacement treatment of Morquio A patients, harmonizing recommendations from published guidelines with the real-life clinical practice in the Central and South-Eastern European region.

Participants: The Consensus Group, convened by 8 Steering Committee (SC) members from 7 Central and South-Eastern European countries, consisted of a multidisciplinary group of 17 experts in the management of MPS in Central and South-Eastern Europe.

Consensus process: The SC met in a first virtual meeting with an external scientific coordinator, to discuss on clinical issues to be analyzed in guidance statements. Statements were developed by the scientific coordinator, evaluated by the SC members in a first modified-Delphi voting and adapted accordingly, to be submitted to the widest audience in the Consensus Conference. Following discussion and further modifications, all participants contributed to a second round of modified-Delphi voting.

Results: Nine of ten statements, concerning general guidelines for management of MPS IVA patients and specific recommendations for treatment, received final consensus.

Conclusions: European guidelines and evidence-based recommendations for Morquio A patients should be considered in the real life of Central and South-Eastern European countries and adapted to unique clinical practice approaches and criteria for patients' access to treatment and reimbursement in the region.

Keywords: Central and South-Eastern European countries; Elosulfase alfa; Enzyme replacement therapy; Morquio syndrome A; Mucopolysaccharidosis IVA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Metabolism, Inborn Errors
Consensus
Enzyme Replacement Therapy
Humans
Isovaleryl-CoA Dehydrogenase / deficiency
Mucopolysaccharidoses* / drug therapy
Mucopolysaccharidosis IV* / drug therapy

Substances

Isovaleryl-CoA Dehydrogenase

Supplementary concepts

Acidemia, isovaleric