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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Analysis of fatal outcomes of patients with mucopolysaccharidosis type II according to the Russian mucopolysaccharidosis registry
Natalia Buchinskaya, Anastasia Vechkasova, Nato Vashakmadze, Leyla Namazova-Baranova, Dmitry Ivanov, Ekaterina Zakharova, Sergei Kutsev, Mikhail Kostik
Natalia Buchinskaya, Mikhail Kostik, Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Sankt-Peterburg, Russia
Natalia Buchinskaya, Anastasia Vechkasova, Clinical Genetics, Saint-Petersburg State Medical Diagnostic Center, Saint Petersburg 194044, Sankt-Peterburg, Russia
Nato Vashakmadze, Leyla Namazova-Baranova, Institution of the Maternity and Childhood, Pirogov Russian National Research Medical University, Moscow 117513, Moskva, Russia
Nato Vashakmadze, Leyla Namazova-Baranova, Department of the Orphan Diseases, Research Institute of Pediatrics and Children's Health in Petrovsky National Research Centre of Surgery, Moscow 119435, Moskva, Russia
Dmitry Ivanov, Department of Neonatology, Saint Petersburg State Pediatric Medical University, Saint Petersburg 194100, Sankt-Peterburg, Russia
Ekaterina Zakharova, Sergei Kutsev, Molecular and Genetic Diagnostics, Federal State Budgetary Scientific Institution, Research Center for Medical Genetics, Moscow 115478, Moskva, Russia
Author contributions: Buchinskaya N, Zakharova E, Kutsev S, Kostik M concept of the article; Buchinskaya N, Kostik M design of the study; Vashakmadze N, Namazova-Baranova L, Zakharova E, Kutsev S, Kostik M supervision; Zakharova E, Kutsev S, Vashakmadze N resources; Buchinskaya N, Vechkasova A materials; Buchinskaia N, Vechkasova A data collection and/or processing; Buchinskaya N, Kostik M analysis and/or interpretation; Buchinskaya N, Vechkasova A literature search; Buchinskaya N, Vechkasova A, Kostik M writing; Vashakmadze N, Namazova-Baranova L, Ivanov D, Zakharova E, Kutsev S critical review. All authors were involved in drafting or revising the article critically for important intellectual content, and all authors approved the final version to be published.
Institutional review board statement: The study was approved by the Ethics Committee of Saint-Petersburg State Pediatric Medical University (protocol #1 from 19.01.2009).
Informed consent statement: Informed consent was obtained from all subjects involved in the study.
Conflict-of-interest statement: All authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Data sharing statement: The original contributions presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Mikhail Kostik, MD, PhD, Professor, Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg 194100, Sankt-Peterburg, Russia.
kost-mikhail@yandex.ru
Received: December 31, 2024
Revised: April 1, 2025
Accepted: April 9, 2025
Published online: September 9, 2025
Processing time: 170 Days and 2.9 Hours
BACKGROUND
Mucopolysaccharidosis type II (MPS II) is a chronic inherited disease with multiorgan involvement, a progressive course, and restricted life expectancy.
AIM
To evaluate the predictors of fatal outcomes in MPS II patients.
METHODS
In the retrospective cohort study, the clinical, laboratory data and enzyme replacement therapy (ERT) (84.2%) of about 160 patients were extracted and analyzed from the Russian MPS II registry, with death as a primary outcome. We compared patients who died (n = 20; 12.5%) with severe form (n = 13; 68.4%) and attenuated form (n = 6, 31.6%) to 140 alive patients.
RESULTS
Fatal outcomes occurred in 5%, 35%, 20%, and 40% of patients before 10, 10-14, 15-19, and ≥ 20 years. The most common causes of death were cardiovascular (29.4%), respiratory failure (17.6%), including pneumonia (17.6%), and their associations (17.6%) and MPS II progression (11.8%). Acute or chronic respiratory failure was in 53%. Died patients had higher birth weight, higher age of diagnosis, and start of ERT. Hydrocephalus, hydrocephalus bypass surgery, epilepsy, difficulty swallowing, and impaired movement after 12 years of age were significantly more common in the deceased patients. Cox regression analysis has revealed the following time-dependent covariates of the lethal outcome: 1st-year psychomotor development delay, delayed mental and speech development, hydrocephalus, swallow disorders, impossible walking at age > 12 years, respiratory disorders, tracheostomy, neuronopathic form.
CONCLUSION
Increased birth weight, delayed diagnosis and the start of ERT, and development of neuronopathic form with impossible walking after 12 years were the main predictors of the fatal outcome.
Core Tip: Mucopolysaccharidosis type II is a rare lysosomal storage disease characterized by the progression of multiorgan dysfunction and increased mortality rates. The assessment of the death outcomes might improve the survival of these patients. High birth weight, delayed diagnosis, delayed enzyme replacement treatment, any signs of central nervous system involvement, and progressive impossibility of independent walking were the main predictors of the fatal outcome.
