P-17

Hunter syndrome, the most prevalent mucopolysaccharidosis in portugal

Sónia Rocha^I; Carla Caseiro^I; Isaura Ribeiro^I; Eugénia Pinto^I; Célia Ferreira^I; Helena Ribeiro^I; Elisabete Silva^I; Fernanda Pinto^I; Sara Pacheco^I; Domingos Sousa^I; Francisco Laranjeira^I; Lúcia Lacerda^I

^IUnidade de Bioquímica Genética, Centro de Genética Médica Doutor Jacinto Magalhães, Centro Hospitalar do Porto E.P.E., Porto, Portugal

sonia.rocha@chporto.min-saude.pt

Introduction: Lysosomal  storage  diseases  (LSD)  is a group of rare diseases which involves more than 50 inherited metabolic diseases, being Hunter disease Mucopolysaccharidosis type II (MPS  II)-  MIM  309900, an inherited X-linked LSD. MPS II is due to iduronate-2-sulfatase (IDS) enzymatic deficiency, that leads to impaired hydrolyses of terminal iduronate 2-sulfate esters into heparan and dermatan sulfate. More than 300 mutations have been reported in IDS gene, located at Xq28, and MPS II has an estimated prevalence of 1 in  170  000  male  live  births. As well as in other MPS disorders, there is a wide clinical variability, ranging from mild to severe clinical phenotype. The availability of enzyme replacement therapy improves many of the symptoms and signs of the disease.

Aim: To report the MPS II prevalence in the Portuguese population and present data from enzyme replacement in treated patients.

Methods: MPS II diagnosis as a three steps analytical approach: screening for quantitative and qualitative urinary glycosaminoglicans accumulation, definitive diagnosis iduronate-sulphatase activity determination in blood or cultured fibroblasts and genotype identification by IDS gene sequencing to ascertain causal mutations.

Results: MPS II is the most prevalent MPS in Portugal. Since 1984, 33 index patients, belonging to 28  families, were diagnosed and 8 of them were submitted to enzyme replacement therapy. Apparently clinical variability among MPS II patients is a mere reflection of molecular heterogeneity, as patients with an IDS gene complete deletion seem to have a more severe form of the disease. A more profound clinical evaluation is required as, until now, no female patients have diagnosed.

Conclusions: Some LSD have a overlapping clinical phenotype with MPS. However, clinicians faced with male affected members in different family generations, should consider MPS II as the first hypothesis in the differential diagnosis. Once the genotype has been ascertained, genetic counseling should include female carrier identification in the affected families. Although the incidence of these genetic diseases is quite low, their combined incidence is 1 in 7000 births, which is in the range considered to be feasible for a newborn screening.