Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program.

The impact of galsulfase enzyme replacement therapy in patients with mucopolysaccharidosis (MPS) VI with phenotypes at either end of the disease spectrum was evaluated. The MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A subanalysis of the CSP was performed in patients with pretreatment urinary glycosaminoglycan (uGAG) levels <100 µg/mg and ≥200 µg/mg creatinine (low- and high-uGAG) who had received galsulfase for ≥6 months. uGAG, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function measures, height/growth, cardiac function, and safety were evaluated. Patients with a high-uGAG level at pre-treatment baseline (N = 68) showed greater impairments in endurance and pulmonary function than those with low-baseline uGAG levels (N = 39). From pre-treatment baseline, the distance walked on the 6MWT in the low- and high-uGAG groups increased by a mean (±SD) of 49 (±151) meters and 42 (±165) meters (median follow-up 5.5 and 7.7 years), respectively. The number of stairs/min climbed in the 3MSCT in the low- and high-uGAG groups increased by a mean of 18 (±33) and 30 (±45) (median follow-up 2.8 and 3.5 years), respectively. Overall, pulmonary function remained unchanged for both groups. No impact was seen on cardiac function. Galsulfase was generally well tolerated in both groups, with most adverse events being MPS-related complications unrelated to galsulfase. Results of this CSP sub-analysis suggest that galsulfase stabilizes MPS VI in the long-term and has an acceptable safety profile, regardless of baseline disease severity.

Paediatric dilated cardiomyopathy: clinical profile and outcome. The experience of a tertiary centre for paediatric cardiology.

Dilated cardiomyopathy is the most common form of cardiomyopathy in the paediatric population and an important cause of heart transplantation in children. The clinical profile and course of dilated cardiomyopathy in children have been poorly characterised. A retrospective review of 61 patients (37 female; 24 male) diagnosed with dilated cardiomyopathy from January, 2005 to June, 2012 at a single institution was performed. The median age at diagnosis was 15 months. Heart failure was present in 83.6% of patients and 44.3% required intensive care. The most prevalent causes were idiopathic (47.5%), viral myocarditis (18.0%) and inherited metabolic diseases (11.5%). In viral myocarditis, Parvovirus B19 was the most common identified agent, in concurrence with the increasing incidence documented recently. Inherited metabolic diseases were responsible for 11.5% of dilated cardiomyopathy cases compared with the 4-6% described in the literature, which reinforces the importance of considering this aetiology in differential diagnosis of paediatric dilated cardiomyopathy. The overall mortality rate was 16.1% and five patients underwent heart transplantation. In our series, age at diagnosis and aetiology were the most important prognosis factors. We report no mortality in the five patients who underwent heart transplantation, after 2 years of follow-up.