T and 1298A>C. We also discuss the management of hyperhomocysteinemia with folic acid supplementation and fortification of folic acid and the impact of a decrease in the prevalence of congenital anomalies and a decline in the incidence of stroke mortality.]]>

This paper presents data collected by a Brazilian center in a multinational multicenter observational study of patients with mucopolysaccharidosis type VI (MPS VI), aiming at determining the epidemiological, clinical, and biochemical profile of these patients. Twenty-eight south-American patients with MPS VI were evaluated through medical interview, physical exam, echocardiogram, electrocardiogram, ophthalmologic evaluation, quantification of glycosaminoglycans (GAGs) in urine, and measurement of the activity of N-acetylgalactosamine-4-sulfatase (ARSB) in leukocytes. 92.9% of patients were Brazilian. Mean age at diagnosis and at evaluation was 48.4 months and 97.1 months, respectively. 88% of patients had onset of symptomatology before the age of 36 months. Consanguinity was reported by 27% of the families. Mean weight and height at birth were 3.481 kg and 51.3 cm, respectively. The most frequently reported clinical manifestations were short stature, corneal clouding, coarse facial features, joint contractures, and claw hands. All patients presented with echocardiogram changes as well as corneal clouding. Mean ARSB activity in leukocytes was 5.4 nmoles/h/mg protein (reference values: 72-174), and urinary excretion of GAGs was on average 7.9 times higher than normal. The number of clinical manifestations did not show a significant correlation with the levels of urinary GAGs nor with the ARSB activity. Also, no significant correlation was found between the levels of urinary GAGs and the ARSB activity. It was concluded that MPS VI has high morbidity and that, when compared with data published in the literature, patients in our study were diagnosed later and presented with a higher frequency of cardiological findings.

For some X-linked disorders the expressivity and penetrance in females are almost similar to those ones found in males. For mucopolysaccharidosis type II (MPS II), there are no studies in the literature trying to identify subtle signs and symptoms of this disease in heterozygotes. The objective of this study was to compare heterozygotes and non-heterozygotes for MPS II, in order to test the hypothesis that heterozygotes may present subtle manifestations of the disease. In this observational and transversal study we collected data on 40 Brazilian women with a positive familial history for MPS II that included clinical and physical exam, karyotype, pattern of X-inactivation, iduronate-2-sulfatase (IDS) activity in leukocytes and plasma, urinary glycosaminoglycans levels, computerized tomography scans (CT) of abdomen and spine, and brain magnetic resonance imaging. The Results showed the following: According to DNA analysis, 22 women were classified as heterozygote and 18 as non-heterozygotes. We did not find any abnormality on physical examination, karyotype, or spine CT. Also the pattern of X-inactivation was not different between the groups. Applying the Bonferroni's correction, both groups were found to differ only in relation to IDS activity in plasma and in leukocyte, which were lower in heterozygotes. In our investigation we did not find any evidence of subtle clinical manifestations of MPS II in heterozygotes. Our findings suggest there is no relation between the absence of clinical signs in these women and the occurrence of a favorable skewing pattern of X-inactivation.

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