Clinical and biochemical studies in mucopolysaccharidosis type II carriers.

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers' and non-carriers' values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

Correlation of MR imaging and MR spectroscopy findings with cognitive impairment in mucopolysaccharidosis II.

BACKGROUND AND PURPOSE: There are no reliable markers to predict neurologic outcome of patients with mucopolysaccharidosis (MPS) II. We hypothesized that brain MR imaging and MR spectroscopy are useful in depicting features related to cognitive impairment (CI) in MPS II. MATERIALS AND METHODS: Nineteen male patients with MPS II were included in this study. They were evaluated through intelligence/developmental tests to be classified in 2 groups: patients with CI (group A) or patients without CI (group B). Brain MR imaging evaluated white matter (WM) lesions, hydrocephalus, and brain atrophy. Voxels from MR spectroscopy (point-resolved spectroscopy TE 30 ms) were positioned in the WM of the deep right frontal lobe and at the gray matter (GM) in the posterior occipital cortex across the midline. Comparison of MR imaging and MR spectroscopy findings between these 2 groups and a control group was performed. RESULTS: The mean age of the patients was 9.6 years (group A, 7.08 years old, 12 patients; group B, 14 years old, 7 patients; P = .076). Brain atrophy and hydrocephalus were more frequently found in group A patients (P=.006 and P=.029, respectively); these patients also presented more severe WM lesions than patients from group B (P=.022). Patients from group A also had a higher myo-inositol (mIns)/creatine (Cr) ratio in the GM (P=.046) and in the WM (P=.032). The choline/Cr and N-acetylaspartate/Cr ratios were similar in both groups. CONCLUSIONS: Our study showed that severe WM lesions, brain atrophy, hydrocephalus, and elevated mIns/Cr were more common in patients with MPS II and with CI.

Association of microcephaly and cafe-au-lait spots in a patient with ring chromosome 12 syndrome.

We describe a patient who was evaluated because of delayed development. The patient had microcephaly and cafe-au-lait spots and the facial features included upward slanting of the palpebral fissures, short nasal bridge and a highly arched palate. In addition the external ears had bilateral over folded helices, there was clinodactyly of the fourth and fifth fingers and multiple cafe-au-lait spots on the back, buttocks and thighs. Chromosomal analysis of peripheral blood showed 46,XY,-r(12)(p13.3q24.33)[73]/45,XY,-12[8]/47,XY,r(12)(p13.3q24.33),+r(12)(p13.3q24.33)[2]. This is the eighth case of a patient with a ring chromosome 12 to be reported so far. The similarity of our patient to those previously described suggests that the ring chromosome 12 syndrome can be delineated as a distinct entity with characteristic clinical features.