RESPONSE TO ENZYME REPLACEMENT THERAPY WITH IDURSULFASE IN 03 BRAZILIAN PATIENTS WITH HUNTER SYNDROME

RESPONSE TO ENZYME REPLACEMENT THERAPY WITH IDURSULFASE IN 03 BRAZILIAN PATIENTS WITH HUNTER SYNDROME

E. S. Santos1; B. K. W. Porto2; I. G. Vilar2, L. S. Athayde2, V. L. Guedes3; S. Beder3

1. Universidade Estadual de Ciências da Saúde de Alagoas – Faculdade de Medicina
2. Hemocentro de Alagoas - HEMOAL

Introduction: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked lysosomal storage disease caused by the deficient activity of the enzyme iduronate-2-sulphatase (IDS) which leads to intralysosomal accumulation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate in cells of different tissues resulting in chronic, progressive multi-organ disease. Its incidence ranges from 1 in 33.750 to 1 in 160.250 male newborns. The main clinical manifestations are: coarse fascies, disostosis multiplex, short stature, joint contractures. Neurological impairment may be present in the severe form. In most cases the cause of death is due to cardiorespiratory failure secondary to cardiovascular involvement and/or upper airway obstruction. Enzyme replacement therapy (ERT) with idursulfase (Elaprase®) has been available as a new treatment for MPS II patients.

Aim: Report the response to ERT with idursulfase in 03 MPS II patients from Alagoas State, (Northeast of Brazil).

Methods: All patients had the MPS II diagnosis confirmed by urinary GAG analysis and IDS activity. Clinical evaluation was performed during the last October/2008 infusion and the results were compared to the baseline ones.

Results: Patient 1 (male, 12 years old) and Patient 2 (male, 20 years old) were mildly affected and both have received 190 weekly infusions of idursulfase. Patient 3 (male, 11 years old) was severely affected and has been on ERT with idursulfase for 25 weeks. All patients have shown improvements in dismorphic features (coarse fascies, hair and skin), liver and spleen sizes, joint contractures, walking, breathing and sleeping patterns. Consequently, a global improvement in the patients’ quality of life has been achieved. However in patients 1 and 2 the valvular diseases have worsened while in patient 3 it has been inalterated. Patient 3 has not shown any CNS improvement.

Conclusions: ERT with idursulfase has improved the somatic features, mobility and breathing patterns in all the patients studied. Patient 3 has not shown any significant improvement in CNS. The reason for that is probably because idursulfase does not cross the bood-brain barrier. The progression of valvular disease in patients 2 and 3 might be related to the natural progress of a valvular disease once installed. Further studies on the evolution of heart disease and CNS envolvement in MPS II must be performed and the Hunter Outcome Survey (HOS) can be a useful tool.

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