Demographic, clinical, and ancestry characterization of a large cluster of mucopolysaccharidosis IV A in the Brazilian Northeast region.

Mucopolysaccharidosis (MPS) IVA is a rare autosomal recessive disease with a highly variable distribution worldwide. Discrepancies in the incidence of MPS IVA among populations of different ethnicities are mostly attributed to founder effects. Demographic and clinical data from 28 MPS IVA patients, followed at a single center, and ancestry (Y chromosome and mitochondrial markers) of a subsample of 17 patients, most with the p.Ser341Arg (c.1023C>G) mutation were analyzed. Parental consanguinity was observed in 15/20 couples; a rare homozygous N-acetylgalactosamine-6-sulfatase (GALNS) mutation was found in 7/16 families with intra-familial phenotypic heterogeneity. Paternal ancestry was 94.2% (16/17) European, 5.8% (1/17) African, and 0% Amerindian. The European paternal haplogroups R1a, R1b, and R* accounted for 94.2% (16/17) of the patients. The R1b haplogroup, identified in 59% (10/17) of the patients, is frequently found in populations from the Iberian Peninsula. European, Amerindian, and African maternal ancestry was observed in 46.9% (8/17), 35.4% (6/17), and 17.7% (3/17) of the patients, respectively. Study of a cluster of MPS IVA patients from Northeastern Brazil, with high parental consanguinity and phenotypic heterogeneity showed predominantly European parental ancestry. This ancestry finding corroborates historical data on the local settlement, formed predominantly by European men.

A second reported malignancy in a patient with Morquio syndrome

Morquio syndrome is a rare lysosomal storage disease that affects multiple organ systems. However, it is rarely associated with malignancy. We present the case of a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma. This case also demonstrates two other findings that have not been previously described in patients with Morquio syndrome - malrotation of brainstem and cerebellum, without clinical neurologic deficit, and persistence of fetal lobulation in the kidneys.

Cytogenetic biomonitoring in mucopolyssacharosis I, II and IV patients treated with enzyme replacement therapy.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate genotoxicity and mutagenicity in peripheral blood and buccal mucosal cells in mucopolysaccharidosis (MPS) I, II or VI patients. METHODS: A total of 12 patients with MPS type I, II and VI attended at the Institute of Genetics and Inborn Errors of Metabolism treated with enzyme replacement therapy (ERT) and 10 healthy control volunteers were included in this study. Mechanically exfoliated cells from cheek mucosa (left and right side) were used to micronucleus test and single cell gel (comet) assay in peripheral blood cells. RESULTS: The results of this study detected the presence of genetic damage in peripheral blood for all individuals with MPS treated with ERT, regardless of type of MPS as depicted by tail moment results. In addition, an increased number of micronucleated cells were found in buccal cells of MPS type II patients. It was also observed an increase of other nuclear alterations closely related to cytotoxicity as depicted by the frequency of pyknosis, karyolysis and karyorrhexis in buccal mucosa cells of MPS VI patients (p < 0.05). CONCLUSION: Taken together, such results demonstrate that metabolic alterations induced by the enzymatic deficiency characteristic of MPS associated with ERT therapy can induce genotoxicity and mutagenicity in peripheral blood and buccal mucosa cells, respectively. This effect appears to be more pronounced to MPS II.

Presentación de un caso clínico de mucopolisacaridosis Tipo IV, síndrome de Morquio / Presentation of a clinical case of mucopolysaccharidosis type IV, Morquio syndrome

Se presenta el caso de un paciente de 16 años de edad, con el diagnostico de mucopolisacaridosis (MPS) tipo IV-A, con una breve revisión teórica del curso y progresión crónica de esta enfermedad multi-sistémica, que se manifiesta con amplia signo sintomatología, hallazgos de laboratorio y anomalías radiológicas. El objetivo es documentar el caso y difundir a la comunidad médica boliviana, la importancia de los errores innatos del metabolismo, consideradas enfermedades "raras", que a criterio nuestro, sufren un sub-diagnóstico debido a las pocas publicaciones científicas sobre el tema en el medio.

We report the case of a patient 16 years old with a diagnosis of mucopolysaccharidosis (MPS) type IV- A, with a brief theoretical review of chronic course and progression of this multisystem disease, which manifests with extensive signs symptoms, findings are presented, with laboratory and radiological reported abnormalities. The aim is to document the event and communicated to Bolivian medical community, the importance of inborn errors of metabolism, considered "rare" diseases, which in our opinion; suffer a sub- diagnosis because of the few Bolivian scientific publications on the topic.

Novel beta-galactosidase gene mutation p.W273R in a woman with mucopolysaccharidosis type IVB (Morquio B) and lack of response to in vitro chaperone treatment of her skin fibroblasts.

The patient is a 24-year-old woman who first came for consultation at age 10 years. Based on clinical phenotype and thin-layer chromatography of urinary oligosaccharides, peripheral leukocytes were sent for beta-galactosidase assay. This testing showed a deficiency in enzyme activity, and gene mutation analysis identified a previously reported mutation p.H281Y (875C > T) and a novel mutation p.W273R (817T > C). Unlike previously reported patients, mutant enzymes in this patient's cultured skin fibroblasts did not respond to treatment with a chaperone compound, N-octyl-4-epi-beta-valienamine.