PURPOSEThis guideline is intended as an educational resource. It highlights current practices and therapeutic approaches to the diagnosis and management of GSD I and its early and longterm complications.

No abstract

Increased transforming growth factor beta (TGF-β) signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS)1-4. However, the location and character of many of the causal mutations in LDS would intuitively infer diminished TGF-β signaling5. Taken together, these data have engendered controversy regarding the specific role of TGF-β in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm6-8. We identified causative variation in 10 patients with SGS in the proto-oncogene SKI, a known repressor of TGF-β activity9,10. Cultured patient dermal fibroblasts showed enhanced activation of TGF-β signaling cascades and increased expression of TGF-β responsive genes. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in SGS patients. These data support the conclusion that increased TGF-β signaling is the mechanism underlying SGS and contributes to multiple syndromic presentations of aortic aneurysm.

Purpose:In this study, we aimed to describe the natural history of mucopolysaccharidosis I.Methods:Data from 1,046 patients who enrolled in the MPS I Registry as of August 2013 were available for descriptive analysis. Only data from untreated patients and data prior to treatment for patients who received treatment were considered. Age at symptom onset, diagnosis, and treatment initiation were examined by geographic region and phenotype (from most to least severe: Hurler, Hurler–Scheie, and Scheie). For each symptom, frequency and age at onset were examined.Results:Natural history data were available for 987 patients. Most patients were from Europe (45.5%), followed by North America (34.8%), Latin America (17.3%), and Asia Pacific (2.4%). Phenotype distribution was 60.9% for Hurler, 23.0% for Hurler–Scheie, and 12.9% for Scheie (3.2% undetermined) syndromes. Median age at symptom onset for Hurler, Hurler–Scheie, and Scheie syndromes was 6 months, 1.5 years, and 5.3 years, respectively; median age at treatment initiation was 1.5 years, 8.0 years, and 16.9 years, respectively. Coarse facial features and corneal clouding were among the most common symptoms in all three phenotypes.Conclusion:A delay between symptom onset and treatment exists, especially in patients with attenuated mucopolysaccharidosis I. A better understanding of disease manifestations may help facilitate prompt diagnosis and treatment and improve patient outcomes.

No abstract