Initial report from the Hunter Outcome Survey

Abstract

on behalf of the HOS InvestigatorsPurpose: Hunter syndrome (Mucopolysaccharidosis II) is a rare, X-linked disorder of glycosaminoglycan metabolism. It is caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase, and in affected patients glycosaminoglycan accumulates in lysosomes of various tissues and organs and contributes to the pathophysiology of Hunter syndrome. The Hunter Outcome Survey (HOS) was established to better describe the natural history of this disorder and to evaluate the long-term effect of enzyme replacement therapy. Methods: HOS is an international, multicenter, long-term observational survey that will collect data on participating patients with a confirmed diagnosis of Hunter syndrome. Data will be collected during regular physician examinations and entered into an electronic database. Examples of observations include vital signs, laboratory values, signs and symptoms of organ involvement, and the results of selected functional tests (e.g., audiometry, echocardiogram, joint mobility, etc.). Results: As of May 15, 2007, 263 patients from 16 countries have enrolled in HOS; 24% of these patients were currently being treated with enzyme replacement therapy. The median age at enrollment was 12.2 years. The median age of onset of symptoms and diagnosis of Hunter syndrome were 1.5 and 3.5 years, respectively. Otitis media and abdominal hernia were the earliest presenting symptoms. Facial dysmorphism and hepatosplenomegaly were demonstrated by 95% and 89% of patients, respectively. Conclusions: HOS will be a valuable resource for enhancing the understanding of Hunter syndrome and will provide important information about the natural history of the disease and the role of enzyme replacement therapy in its treatment. Patients and their physicians should be encouraged to participate. Genet Med 2008:10(7):508 -516.

Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age

“…In addition, there are non-controlled patient registry data suggesting that the safety profile of idursulfase is similar in younger and older patients in clinical practice. A retrospective study using data from the Hunter Outcome Survey (HOS), a voluntary patient registry for patients with MPS II regardless of treatment status (Wraith et al 2008), evaluated the safety and effectiveness of idursulfase in 124 patients younger than 6 years and compared these findings with those seen in 289 older patients (Muenzer et al 2011a). The mean age at start of ERT in the younger group was 3.6 AE 1.6 years.…”

“…The storage materials, heparan sulfate and dermatan sulfate, accumulate within lysosomes and are present in plasma, urine, and cerebral spinal fluid (Neufeld and Muenzer 2001;Tomatsu et al 2005). Although patients with MPS II appear normal at birth, the disease is progressive and signs and symptoms usually become apparent during early childhood (Wraith et al 2008). Early signs and symptoms of the disease may include dysmorphic facial features, airway obstruction, chronic rhinorrhea, recurrent respiratory infections, recurrent ear infections, hearing loss, hernia, hepatosplenomegaly, chronic watery diarrhea, and joint stiffness and contractures .…”

Survival in idursulfase‐treated and untreated patients with mucopolysaccharidosis type II: data from the Hunter Outcome Survey (HOS)

“…Deficiency in I2S activity leads to gradual accumulation of glycosaminoglycans in organs and tissues throughout the body. The resulting signs and symptoms can include both somatic and neurological involvement and are progressive in nature (Neufeld and Muenzer 2001;Wraith et al 2008a;b). Those affected by MPS II are almost always males (Neufeld and Muenzer 2001), with an estimated incidence of 0.6-1.3 per 100,000 live male births (Meikle et al 1999;Poorthuis et al 1999;Baehner et al 2005;Tylki-Szymanska 2014).…”

“…Somatic involvement in patients without cognitive impairment can range from being severe with early onset to much less severe with later onset (Young et al 1982;Young and Harper 1983;Neufeld and Muenzer 2001;Schwartz et al 2007;Wraith et al 2008b); this group of patients usually exhibits minimal or no neurological involvement. Management of patients with MPS II requires a multidisciplinary approach involving a range of specialties such as cardiology, neurology, psychology, pulmonology and orthopaedics (Wraith et al 2008a;Muenzer et al 2009;Scarpa et al 2011). Disease-specific treatment in the form of enzyme replacement therapy (ERT) with recombinant I2S (idursulfase [Elaprase®]; Shire, Lexington, MA, USA) became available in the USA in 2006 and Europe in 2007, and alleviates many of the somatic signs and symptoms of the disorder (Muenzer et al 2011); before this, symptomatic management was the only possible treatment approach.…”

Otolaryngological findings in mucopolysaccharidosis

“…[16][17][18] Recent studies from Germany and the Netherlands report an incidence of one case in 140,000-330,000 live births, and 1.3 cases per 100,000 male births. [19,20] The severe form of Hunter syndrome is typically diagnosed in children aged between 2-4 years. The attenuated form of Hunter syndrome may not be diagnosed until the teenage years or well into adulthood.…”