Long-term open-label phase I/II extension study of intrathecal idursulfase-IT in the treatment of neuronopathic mucopolysaccharidosis II.

Purpose: Intrathecal (IT) idursulfase-IT for the treatment of cognitive impairment is being investigated in pediatric patients with neuronopathic mucopolysaccharidosis II (MPS II) in addition to intravenous idursulfase. In this article, we report the findings for 54 months of idursulfase-IT treatment in an ongoing phase I/II extension trial (NCT01506141).

Methods: A total of 15 male participants with neuronopathic MPS II (aged 3-11 years at enrollment) who were previously treated with intravenous idursulfase entered the extension study.

Analysis of the caregiver burden associated with Sanfilippo syndrome type B: panel recommendations based on qualitative and quantitative data.

Background: Sanfilippo syndrome type B (Sanfilippo B) belongs to a group of rare lysosomal storage diseases characterized by progressive cognitive decline from an early age, acute hyperactivity, and concomitant somatic symptoms. Caregivers face a unique set of challenges related to the complex nature of Sanfilippo B, but the burden and impact on quality of life (QoL) of caregivers is poorly defined and best practice guidance for clinicians is lacking.

Methods: An international clinical advisors meeting was convened to discuss key aspects of caregiver burden associated with Sanfilippo B based on findings from qualitative and quantitative research undertaken to identify and quantify the nature and impact of the disease on patients and caregivers.

A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II.

Purpose: Approximately two-thirds of patients with the lysosomal storage disease mucopolysaccharidosis II have progressive cognitive impairment. Intravenous (i.v.

MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function.

Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome.

Purpose: This study evaluated the safety and effectiveness of long-term enzyme replacement therapy with idursulfase (recombinant human iduronate-2-sulfatase) in patients with Hunter syndrome.

Methods: All 94 patients who completed a 53-week double-blinded study of idursulfase enrolled in this open-labeled extension study and received intravenous idursulfase at a dose of 0.5 mg/kg weekly for 2 years, and clinical outcomes and safety were assessed.

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome).

Purpose: To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II.

Methods: Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.

The impact of screening for propionic and methylmalonic acidaemia.

Unlabelled: The outcome of the severe variants of propionic and methylmalonic acidaemia is not good. Patients with these disorders have increased concentrations of propionylcarnitine and using tandem mass spectrometry to detect this compound, it is possible to screen in the newborn period. Various criteria have been used to identify the patients but only a small number of patients have been diagnosed so far and some have been missed.