Mortality and cause of death in mucopolysaccharidosis type II—a historical review based on data from the Hunter Outcome Survey (HOS)

Abstract

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a progressive, multisystemic disease caused by a deficiency of iduronate-2-sulfatase. Patients with the severe form of the disease have cognitive impairment and typically die in the second decade of life. Patients with the less severe form do not experience significant cognitive involvement and may survive until the fifth or sixth decade of life. We studied the relationship of both severity of MPS II and the time period in which patients died with age at death in 129 patients for whom data were entered retrospectively into HOS (Hunter Outcome Survey), the only large-scale, multinational observational study of patients with MPS II. Median age at death was significantly lower in patients with cognitive involvement compared with those without cognitive involvement (11.7 versus 14.1 years; p = 0.024). These data indicate that cognitive involvement is indicative of more severe disease and lower life expectancy in patients with MPS II. Median age at death was significantly lower in patients who died in or before 1985 compared with those who died after 1985 (11.3 versus 14.1 years; p alpha 0.001). The difference in age at death between patients dying in or before, relative to after, the selected cut-off date of 1985 may reflect improvements in patient identification, care and management over the past two decades. Data from patients who died after 1985 could serve as a control in analyses of the effects of enzyme replacement therapy with idursulfase on mortality in patients with MPS II.

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

“…Individuals with severe cognitive impairment typically die in their second decade, usually as a result of respiratory obstruction and/or cardiac failure (Neufeld and Muenzer 2001;Wraith et al 2008b;Jones et al 2009). Those who experience only somatic involvement may survive into their fifth or sixth decade (Neufeld and Muenzer 2001;Wraith et al 2008b;Jones et al 2009). Survival has improved since 1985, hypothesized to be a result of improvements in supportive care and an increased awareness and understanding of the disease; the latter factors may have led to increased recognition of less severely affected patients and thus an increase in overall life expectancy (Jones et al 2009;Muenzer et al 2009;Scarpa et al 2011).…”

“…Those who experience only somatic involvement may survive into their fifth or sixth decade (Neufeld and Muenzer 2001;Wraith et al 2008b;Jones et al 2009). Survival has improved since 1985, hypothesized to be a result of improvements in supportive care and an increased awareness and understanding of the disease; the latter factors may have led to increased recognition of less severely affected patients and thus an increase in overall life expectancy (Jones et al 2009;Muenzer et al 2009;Scarpa et al 2011). The impact of ERT with idursulfase on survival and causes of death in patients with MPS II has not yet been evaluated.…”

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

“…This includes neurological manifestations such as communicating hydrocephalus and carpal tunnel syndrome . Such patients may live into the fifth or sixth decade of life or longer (Jones et al 2009). …”

Successful Noninvasive Ventilation and Enzyme Replacement Therapy in an Adult Patient with Morbus Hunter

“…Typical changes in the physiognomy occur in childhood, with coarseness in the facial features resulting from the accumulation of GAG: nose with flattened bridge, thick lips, large head, prominent forehead, short neck, widely spaced teeth, as well as frizzy hair and thickened skin. In addition, other characteristic changes or diseases as otitis, hernia, diseased heart valves, hepatosplenomegaly, joint stiffness and kyphoscoliosis are often observed (Beck 2011;Martin et al 2008;Jones et al 2009;Harper 1982, 1983). Respiratory symptoms are typical and a common cause of clinical deterioration particularly as the disease progresses and in adulthood.…”

“…Attenuated cases with almost normal life expectancy have also been described, although very rarely (Young and Harper 1982;Jones et al 2009). Only around 10% of all Hunter patients reached the age of 25 before the introduction of enzyme replacement therapy (Wraith et al 2008;Jones et al 2009). …”