Impact of ERT and Follow up of 17 Patients from the Same Family with Mild form of MPS II

Abstract Background: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate-2- sulfatase (IDS), leading to progressive accumulation of glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefit for patients, retarding natural progression of the disease.Results: We evaluated 17 patients from the same family with a mild form of MPS type II; proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgery complications shortly after the procedure. Nevertheless, subsequently to his tragic death, 16 affected male relatives were detected after biochemical tests identifying low or absent activity of IDS enzyme and confirmed by molecular analysis of IDS gene.Following diagnosis, different options of treatment were decided: 6 patients startedERT with Elaprase® (Idursulfase) soon after, while other 10 remained without ERT;eventually, 4 patients among the latter group began ERT with Hunterase® (Idursulfase Beta). None presented adverse effects to neither forms of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients are alive with independent style of life.Conclusion: Here we report the variable progress of disease with and without ERT in a large Brazilian family with attenuated form of MPS II, harboring the same missense variant in the IDS gene.