Mucopolysaccharidosis type III in Portugal

Introduction: Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a rare autosomal recessively inherited disorder composed at least by four different subtypes: type A (OMIM # 252900), type B (OMIM # 252920), type C (OMIM # 252930) and type D (OMIM # 252940). Each subtype is caused by a deficiency in a different enzyme involved in the catabolic pathway for heparan sulfate. From the clinical point of view, type III patients can be classified within the MPS neurodegenerative phenotype, given visceromegaly, coarse facies, joint disease and bone dysplasia are relatively mild and progresses steadily. Behavioural disturbances and hyperactivity are often reported in the early stages of the disease. Objectives: The aim of this study is to draw the attention to the several subtypes which may be diagnosed within type III MPS, pointing out for mucopolysacharidosis-like patients with unclear etiology. Methods: MPS type III patients are diagnosed by the quantification of GAG heparan sulfate in urine, identification of the enzymatic deficiency in peripheral blood and gene sequencing for causal mutations. Results: From 34 MPS type III families, 4 patients were found to be IIIA, 24 IIIB and 6 IIIC. Type IIIB is the most common, accounting for 70% of all Portuguese cases with MPS III. Conclusions: Biochemical and molecular characterization allows carrier identification and informed family planning decisions. A negative diagnosis for subtype A to D does not rule out the disease and those patients with a high clinical suspicion are currently further tested for a recently proposed subtype, MPS IIIE.