Cardiac involvement in MPS patients: incidence and response to therapy in an Italian multicentre study

• Published in: Orphanet journal of rare diseases 2022-06, Vol.17 (1), p.1-251, Article 251
• Main Authors: Sestito, Simona, Rinninella, Giada, Rampazzo, Angelica, D'Avanzo, Francesca, Zampini, Lucia, Santoro, Lucia, Gabrielli, Orazio, Fiumara, Agata, Barone, Rita, Volpi, Nicola, Scarpa, Maurizio, Tomanin, Rosella, Concolino, Daniela
• Format: Article
• Language: English
• Subjects: Age groups; Aorta; Cardiovascular disease; Cardiovascular diseases; Care and treatment; Complications and side effects; Diagnosis; Distribution; Enzyme replacement therapy (ERT); Enzymes; Genetic diversity; Genotype & phenotype; Glycosaminoglycans; Glycosaminoglycans (GAGs); Heart; Heart diseases; Heart involvement; Long-term effects; Lysosomal storage diseases; Medical research; Mucopolysaccharidoses (MPS); Mucopolysaccharidosis; Pathology; Patient outcomes; Patients; Phenotypes; Rare diseases; Rheumatic heart disease; Risk factors; Stem cell transplantation; Valvulopathies
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-022-02396-5

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders caused by the deficit of lysosomal hydrolases involved in the degradation of glycosaminoglycans (GAGs). The course is chronic and progressive, with multisystemic involvement that often leads to cardiovascular disease. We describe the overall incidence and type of cardiac damage in a cohort of Italian MPS patients, and their progression over time, also with reference to treatment efficacy in patients under Enzyme Replacement Therapy (ERT). Moreover, we report a possible association between genetic variants and cardiac phenotype in homozygous and hemizygous patients to understand whether a more aggressive clinical phenotype would predict a greater cardiac damage. Our findings confirm that cardiac involvement is very common, already at diagnosis, in MPS VI (85.7% of our cohort), and in MPS II (68% of our cohort) followed by MPS I subjects (55% of our cohort). The most frequent heart defect observed in each MPS and at any time-point of evaluation was mitral insufficiency; 37% of our patients had mitral insufficiency already at diagnosis, and 60% at post-ERT follow-up. After at least six years of treatment, we observed in some cases (including 6 MPS II, 2 MPS IV and 2 MPS VI) a total regression or improvement of some signs of the cardiac pathology, including some valve defects, though excluding aortic insufficiency, the only valvulopathy for which no regression was found despite ERT. The general clinical phenotype proved not to be strictly correlated with the cardiac one, in fact in some cases patients with an attenuated phenotype developed more severe heart damage than patients with severe phenotype. In conclusion, our analysis confirms the wide presence of cardiopathies, at different extent, in the MPS population. Since cardiac pathology is the main cause of death in many MPS subtypes, it is necessary to raise awareness among cardiologists about early cardiac morpho-structural abnormalities. The encouraging data regarding the long-term effects of ERT, also on heart damage, underlines the importance of an early diagnosis and timely start of ERT.