The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis Type I.

A global, observational disease registry has been established to characterize the course of disease and track clinical outcomes in patients with Mucopolysaccharidosis Type I (MPS I), a rare and treatable lysosomal storage disorder. This report outlines procedures for data collection and presents the recommended minimum schedule of assessments that comprise the disease-specific clinical and laboratory parameters that are tracked in the database. Aggregate data are summarized for the first 302 patients enrolled, representing entries from 24 countries. The median current age of the patients is 9.0 years (range: 0.4-64.8). Syndrome diagnoses include 47% Hurler (severe form), 25% Hurler-Scheie (attenuated form with an intermediate phenotype), 13% Scheie (most attenuated form), and 15% unknown. Younger ages at symptom onset and disease diagnosis are associated with the severe Hurler syndrome, but there is overlap among syndromes. Diagnosis was delayed by years to decades in several patients with Hurler-Scheie and Scheie syndromes. Patients with symptom onset before age 5 are more likely to have a gibbus, cognitive impairment, and pneumonia, whereas patients with symptom onset above age 5 are more likely to have carpal tunnel syndrome, myelopathy, and glaucoma. Cardiac valve abnormalities, joint contractures, corneal clouding, and hernia are reported by over 70% of patients regardless of the age of symptom onset. Approximately 80% of the patients have received enzyme replacement therapy, hematopoietic stem cell transplantation, or both. Overall, the MPS I Registry database contains a broad sample of the global patient population, providing a potentially useful tool for expanding knowledge of MPS I and facilitating evidence-based decisions about the optimal means of monitoring and treating affected individuals.

A clinical study of 77 patients with mucopolysaccharidosis type II.

AIM: This study aims to assess the clinical features of 77 South American patients (73 Brazilian) with mucopolysaccharidosis type II (MPS II). METHODS: Details of the patients and their disease manifestations were obtained from a review of medical records, interviews with the patients and/or their families, and physical examination of the patients. RESULTS: Mean birth weight was 3360 g, median age at onset of symptoms was 18 months and median age at diagnosis was 6 years. For the whole sample (median age, 8.2 years; range, 2.8-53.0 years), neurological degeneration, typical pebbly skin lesions, seizures and extensive dermal melanocytosis were found in 23.3, 13.0, 13.0 and 1.3% of the cases, respectively. The most frequently reported echocardiogram abnormality was mitral valve regurgitation. Refraction errors were the most common ophthalmological manifestation. The following characteristics were found to be associated with the severe form of MPS II: earlier age at biochemical diagnosis, higher levels of urinary glycosaminoglycans, language development delay, behavioural disturbances, poor school performance and mental retardation. CONCLUSION: Our results suggest that there is a considerable delay between the onset of signs and symptoms and the diagnosis of MPS II in Brazil (and probably in South America as well), and that many complications of this disease are underdiagnosed and undertreated. Therefore, the implementation of programmes aiming to increase the awareness of the disease, the availability of biochemical diagnostic tests and the provision of better support to affected patients is urgently needed.

Molecular findings in Brazilian patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder of increased bone fragility and low bone mass. Severity varies widely, ranging from intrauterine fractures and perinatal lethality to very mild forms without fractures. Most patients with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes that encode the a chains of type I procollagen, the major protein in bones. Hence, the aim of the present study was to identify mutations in the COL1A1 gene in 13 unrelated Brazilian OI patients. This is the first molecular study of OI in Brazil. We found 6 mutations, 4 of them novel (c.1885delG, p.P239A, p.G592S, p.G649D) and 2 previously described (p.R237X and p.G382S). Thus, the findings show that there are no prevalent mutations in our sample, and that their distribution is similar to that reported by other authors, with preponderance of substitutions for glycine in the triple helix domain, causing OI types II, III and IV.