Analysis of fatal outcomes of patients with mucopolysaccharidosis type II according to the Russian mucopolysaccharidosis registry.

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 ( = 20; 12.5%) with severe form ( = 13; 68.4%) and attenuated form ( = 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: 1-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.