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

Abstract

Background 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. Results 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. Conclusions 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.

Safe and effective liver-directed AAV-mediated homology-independent targeted integration in mouse models of inherited diseases

“…Indeed, MPS VI patients suffer from heart failure, predominantly due to mitral valve insufficiency. 51 A further feature of MPS VI patients is skeletal abnormalities, 49 , 52 which have also been described in the mouse model of MPS VI. 53 Therefore, we assessed if AAV-HITI can improve these disease manifestations.…”

Alpha-mannosidosis: a diagnostic journey in patients with ultra-rare disease

“…Поражение сердца нередко развивается при некоторых лизосомных болезнях накопления, в частности мукополисахаридозах и болезни Фабри, и может быть причиной инвалидизации и смерти. Для мукополисахаридозов, прежде всего VI, II и I типа, характерно развитие митральной недостаточности, которая в итальянском исследовании уже на момент установления диагноза была выявлена у 37% из 60 пациентов с мукополисахаридозами различных типов [11]. Прогрессирующая недостаточность клапанов при этих заболеваниях может потребовать протезирования.…”

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

“…Our search resulted in (at least) 520 MPS-IV patients presenting cardiac symptoms (in some comparative studies in which multiple MPS types were studied together, it was not always possible to determine the exact number of MPS-VI, and thus our count could be slightly underestimated; see Supplementary Table S3). The cardiac symptoms consisted primerily of cardiac valvular disease including VLD, valve thickening, DAR, MVP, AVP, TVP, MVR, ARe, TVR, MI, AI, TI, MVS, TVS and less frequently VSD (intraventricular septal hypertrophy), LHV, HCM and LVCR [497,512,532,540,544,556,564,570,574,579,[589][590][591]596, (Table 6, Supplementary Tables S2 and S3). Cardiac involvement often escalated to congestive HF.…”