No abstract

A high performance liquid chromatography method, adapted from an established urinary sugars method, has been developed for the analysis of a tetraglucose oligomer (Glc(4)) in urine. Pompe disease results from defects in the activity of lysosomal acid α-glucosidase (GAA) with patients typically excreting increased amounts of Glc(4). Rapid determination of GAA in dried blood spots is now possible. However, enzymatic analysis is unable to discriminate between patients with Pompe disease and those individuals harbouring pseudo deficiency mutations. This method was able to quantify Glc(4) levels in all patients analysed with an established diagnosis of Pompe disease, and all controls analysed had Glc(4) levels below the limit of detection for this method. Importantly the method was able to discriminate between an individual known to harbour a pseudo Pompe mutation and patients with Pompe disease, providing a useful supporting test to enzymatic analysis. Sequential measurement of urinary Glc(4) has been proposed to monitor the effects of enzyme replacement therapy (ERT). We observed a clear decrease in Glc(4) levels following commencement of treatment in three patients studied. Additionally, raised levels of Glc(4) were observed in patients with glycogen storage disease (GSD) type Ia and type III suggesting that this method may have applications in other GSDs.

The current treatment of mucopolysaccharidosis type II (MPS II, Hunter syndrome) is enzyme replacement therapy with recombinant idursulfase (Elaprase®). The efficacy of ERT was established based primarily on reduction in urine glycosaminoglycans:creatinine (GAG:Cr) ratio and improvement in a composite score of predicted forced vital capacity (FVC% predicted) and 6-min walk-test distance (6MWT). We retrospectively reviewed these parameters in 11 boys with MPS II treated with idursulfase between April 2007 (or the time of diagnosis) and February 2010. Some results were inconsistent with published trial data, and there was only a small number of analyzable results obtained for the FVC% predicted and 6MWT. A major drawback was the high prevalence of neurological involvement and young age of patients in the study cohort compared with the clinical trials. This study emphasizes the limitations of the current tools utilized to monitor ERT efficacy and MPS II disease burden in clinical practice.

Lumosity is a subscription-based suite of online brain-training games, intended to improve cognitive skills. Due to an influx of products designed to train cognition through games such as Lumosity, it is important to determine their effectiveness for the sake of consumers and for the potential implications of any training effects for theories of transfer of cognitive skills. Two training experiments were conducted using the Lumosity platform. Participants were divided into three groups: those who trained with five attention games in Lumosity (attention group), those who trained with five flexibility games in Lumosity (flexibility group), and an inactive control group. Participants were assessed on accuracy and response time for two cognitive tests of attention (useful field of view and change detection) and two cognitive tests of flexibility (Wisconsin card sort and Stroop) both before and after a training period. In experiment 1, the training period was 3 h spread over four sessions. In experiment 2, the training period was 15 to 20 h spread over an average of 73 sessions. The trained groups did not show significantly greater pretest-toposttest gains than the control group on any measures in either experiment, except in experiment 2 where the flexibility group significantly outperformed the other two groups on Stroop response time and UFOV reaction time. A practical implication concerns the lack of strong evidence for the effectiveness of brain-training games to improve cognitive skills. A theoretical implication concerns the domain specificity of cognitive skill learning from brain training games.

No abstract