Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin America.

Roberto Giugliani,C Araceli Arellano Valdez,Martha Luz Solano Villarreal,Norberto Guelbert,Hernán Amartino,Angelina Acosta,Aída Lemes,Antonieta Mahfoud Hawilou,Mara Lucia Schmitz Ferreira Santos,Ana Maria Martins,Juan Francisco Cabello,Luz Norela Correa Garzón

doi:10.1590/s1415-47572014000300003

Abstract

This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based on screening urinary glycosaminoglycans and confirmation by measuring I2S activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S) (Elaprase(®), Shire) enzyme replacement therapy (ERT), designed to address the underlying enzyme deficiency, is approved treatment and improves walking capacity and respiratory function, and reduces spleen and liver size and urinary glycosaminoglycan levels. Additional measures, responding to the multi-organ manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery, and cardiac valve replacement, should also be considered. Investigational treatment options such as intrathecal ERT are active areas of research, and bone marrow transplantation is in clinical practice. Communication among care providers, social workers, patients and families is essential to inform and guide their decisions, establish realistic expectations, and assess patients' responses.

Highlights

This review summarizes the expertise of a multidisciplinary group of health professionals with extensive experience in Hunter syndrome; the aim is to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available
Mendelsohn and colleagues compared surgical histories of patients with Hunter syndrome enrolled in the Hunter Outcome Survey (HOS), a global registry of patients with Hunter syndrome sponsored by Shire, with those of the general population and found that more than 80% of HOS-enrolled patients required surgical intervention and that 57% had undergone surgical intervention prior to Hunter syndrome diagnosis
After 53 weeks, patients receiving a weekly regimen of idursulfase experienced a statistically significant mean 44.3-m (± 12.3 m) improvement in the 6-minute walk test (6MWT) compared to patients receiving placebo, who experienced a mean improvement of 7.3 m (± 9.5 m) (p = 0.0131)

Summary

Introduction

This review summarizes the expertise of a multidisciplinary group of health professionals with extensive experience in Hunter syndrome; the aim is to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. The mucopolysaccharidoses (MPSs) are inherited metabolic disorders caused by genetic defects that result in the absence or severe deficiency of one of the lysosomal hydrolases responsible for the degradation of glycosaminoglycans (GAGs). Part of the group of lysosomal storage disorders (LSDs), all MPSs are autosomal-recessive, with the exception of Hunter syndrome, or MPS II, which is an X-linked recessive disease (Neufeld and Muenzer, 2001). The abnormal deposition of GAGs alters the architecture and function of cells and tissues, resulting in dysfunction of multiple organs and systems, producing a broad spectrum of chronic and progressive clinical manifestations

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