Prasad, S.

The prevalence and impact of scoliosis in Pompe disease: Lessons learned from the Pompe Registry (Article)

2011-12-01T00:00:00Z

Pompe disease is a rare, autosomal recessive, progressively debilitating, and often fatal neuromuscular disorder. While scoliosis is common in many other neuromuscular disorders, there is little information on its prevalence and impact in Pompe disease. To further our understanding, we performed a cross-sectional analysis of data from the Pompe Registry, a multinational, long-term observational program that contains the largest collection of data in the world of patients with Pompe disease. In this analysis, patients were categorized by age during the natural history period (defined as the time when patients never received enzyme replacement therapy) and by age at onset of symptoms as infants (≤ 0 to < 2. years of age); children (≥ 2 to < 13. years of age); juveniles (≥ 13 to < 20. years of age); and adults (≥ 20. years of age). Scoliosis was defined by clinical assessment, X-ray of the spine, or both. Data on scoliosis were available in the majority of patients enrolled in the registry as of September 2010 (711/873, 81.4%). Scoliosis was present in a third of all patients with scoliosis data (235/711, 33%) in the Pompe Disease Registry. Scoliosis was found more frequently in patients with onset of Pompe symptoms as children (57.0%) and juveniles (52.9%) than in patients with onset of symptoms as adults (24.8%). Only 18.4% (38/206) of patients with onset of symptoms as infants were reported as having scoliosis. Scoliosis was reported in the majority (62.5%) of wheelchair users for all age groups. A larger percentage of patients with scoliosis required respiratory support than patients without scoliosis (44% vs 27.2%, respectively), and pulmonary function in those with scoliosis was consistently reduced in the 3 older age groups compared to those without scoliosis, with the largest differences demonstrated in juveniles. Patients with scoliosis had been diagnosed with Pompe disease for a mean of 1.2 (± 14.34) years before the first reporting of scoliosis. As with other registry analyses, data were collected from multiple sites in different countries and assessments of scoliosis therefore may not be based on consistent criteria. However, the observed occurrence of scoliosis across all age groups of patients with Pompe disease and its association with increased clinical morbidity, underscores the need for clinical assessment of scoliosis in all patients with Pompe disease.

Erratum to "Pompe disease: Design, methodology, and early findings from the Pompe Registry" [Mol. Genet. Metabol. 103 (2011) 1-11] (Article)

2011-11-01T00:00:00Z

Pompe disease: Design, methodology, and early findings from the Pompe Registry (Article)

2011-05-01T00:00:00Z

Pompe disease is an autosomal recessive, progressive, debilitating, and often fatal neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase (GAA). It is characterized by the accumulation of glycogen in muscle tissue that leads to progressive muscle weakness and loss of function. It presents as a broad spectrum of clinical phenotypes, with varying rates of progression, symptom onset, degree of organ involvement, and severity. The Pompe Registry represents worldwide data collection on this rare and clinically heterogeneous disease. This report describes the design, methodology, and early findings from the Registry and presents an overview of the Registry population over a five-year period from its inception in September 2004 through September 2009. Among the 742 patients from 28 countries in the Registry, 70% (517/742) reported symptom onset > 12 months of age and 23% (170/742) reported symptom onset > 12 months of age. Seventy-eight percent (582/742) of registry patients have received enzyme replacement therapy. Overall, Registry data appear to be consistent with smaller natural history studies in terms of symptoms and disease course in classical infantile Pompe disease (> 12 months of age with cardiomyopathy) and late-onset Pompe disease (> 12 months of age). In addition, a subset of patients with symptom onset > 12 months of age do not have cardiomyopathy (14.7%); these patients appear to have a later age at first symptoms and diagnosis than their peers with cardiomyopathy. As the largest dataset on Pompe disease to date, the Pompe Registry will serve to improve recognition of the disease, enhance understanding of the variable disease course, and offer insights into treated and untreated disease course.

Planning the human variome project: The Spain report (Article)

2009-04-01T00:00:00Z

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., micro-arrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008.

case for trade-based development assistance? : Fiji and the sugar protocol (Research Paper)

1997-01-01T00:00:00Z