The natural course and the impact of therapies of cardiac involvement in the mucopolysaccharidoses

TLDR

The study aims to analyze cardiac involvement progression in mucopolysaccharidoses and evaluate the short‑term impact of new therapies, noting that longer follow‑up is required to confirm improvement. Echocardiographic assessment of 57 patients with mucopolysaccharidoses over a median 4.6‑year follow‑up was used to track cardiac involvement. Cardiac involvement rose from 59.6 % to 87.3 % over follow‑up, with severity increasing with age and varying by MPS type; mitral valve lesions were most common, types I and II showed more severe disease, hematopoietic stem‑cell transplantation stabilized progression, but enzyme replacement therapy had no demonstrable effect.

Abstract

To analyze cardiac involvement and its progression in mucopolysaccharidoses, and to assess the short term impact of new therapeutic strategies.We studied echocardiographically 57 patients with various types of mucopolysaccharidoses, specifically types I, II, III, IV and VI, with a median age at the diagnosis of cardiac involvement of 5 years, following them for a median of 4.6 years, with a range from 0.9 to 21.2 years. We used a scoring system, along with the so-called delta score, to quantify the severity of involvement at baseline and at last examination, and to chart their progression over time.Cases with cardiac involvement increased from 59.6% to 87.3% at the last examination. The scores increased with age, and were significantly different according to the specific type of mucopolysaccharidosis. Involvement of the mitral valve was most common, often associated with an aortic valvar anomaly and/or left ventricular hypertrophy. Patients with the first and second types had more severe involvement than those with the third or fourth types. Patients undergoing transplantation of haematopoietic stem cells seem to stabilize after an initial worsening while, in contrast, we were unable to demonstrate an effect of enzyme replacement therapy on the progression of the cardiac disease, possibly because those receiving such treatment had a higher median age, more severe cardiac disease and shorter follow-up.Cardiac involvement was present early in more than a half of the patients identified as having mucopolysaccharidosis, and generally progressed, being more frequent and severe in the first and second types of the disease. Longer follow-up is needed to demonstrate any significant improvement induced by new therapies.