Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease

Abstract

Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symptoms, and disease progression are heterogeneous, and patients may present with many different manifestations to a wide range of specialists. Expertise in diagnosing and managing MPS II varies widely between countries, and substantial delays between disease onset and diagnosis can occur. In recent years, disease-specific treatments such as enzyme replacement therapy and stem cell transplantation have helped to address the underlying enzyme deficiency in patients with MPS II. However, the multisystem nature of this disorder and the irreversibility of some manifestations mean that most patients require substantial medical support from many different specialists, even if they are receiving treatment. This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies.

Take-home message: Expertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan-European recommendations for the diagnosis and management of this life-limiting disease.

Figure 1

Characteristic features of mucopolysaccharidosis type II. Fourteen-year-old boy showing (a) coarsened facial features (including enlarged head, broad nose with flared nostrils, prominent supraorbital ridges, large jowls, thickened lips, and irregular peg-shaped teeth), (b) musculoskeletal manifestations (including short neck, short stature, and joint stiffness [unable to raise arms above head]) and (c) abdominal distension due to hepatomegaly and splenomegaly. (d) Tracheomalacia seen at airway endoscopy. (a)-(b) reproduced with permission from Martin and colleagues [11], Copyright ^© 2008 by the AAP; (a)-(c) courtesy of Professor Joseph Muenzer; (d) courtesy of Dr Iain Bruce.

Figure 2

Diagnostic algorithm for mucopolysaccharidosis type II (MPS II). The 'gold standard' for the diagnosis of MPS II in a male proband is demonstration of deficiency of iduronate-2-sulfatase enzyme activity in leukocytes, fibroblasts, or plasma. Measurement of iduronate-2-sulfatase activity in dry blood spots also represents a valuable method for diagnosis, as no heparin is needed and very little blood is required. GAGs = glycosaminoglycans. IDS = iduronate-2-sulfatase gene. LSD = lysosomal storage disease. MPS = mucopolysaccharidosis. MSD = multiple sulfatase deficiency.

Figure 3

Clinical effects of enzyme replacement therapy (ERT) with idursulfase (0.5 mg/kg weekly) or placebo in patients with mucopolysaccharidosis type II (MPS II). (a) Mean (± SE) change from baseline in distance walked in 6-minute walk test; (b) mean (± SE) change from baseline in percentage of predicted forced vital capacity; (c) mean (± SE) change from baseline in absolute forced vital capacity; (d) mean (± SE) change from baseline in concentration of urine glycosaminoglycans; (e) mean (± SD) growth velocity before and during enzyme replacement therapy; (f) incidence of infusion reactions during treatment with idursulfase. Absolute forced vital capacity is a better measure of respiratory function than percentage of predicted forced vital capacity, as the latter assumes both normal growth and height, which does not apply to patients with MPS II. (a-d) adapted from [34] with permission; (e) reproduced from [37] with kind permission from Springer Science & Business Media; (f) reproduced from [35] with permission. *p = 0.0131; **p = 0.011; ***p < 0.0001, compared with placebo based on analysis of covariance. SD = standard deviation. SE = standard error. ANCOVA = analysis of covariance. FVC = forced vital capacity. ERT = enzyme replacement therapy.

Figure 4

Algorithm for the provision of enzyme replacement therapy (ERT) outside of the hospital setting. ^aPatient aged 5 years or older, with no infusion-related reactions, with stable airway disease and established intravenous access. ^bUnder some circumstances, an environment other than the home, such as school, may be considered as an alternative to the clinic. Adapted from [42] with permission from Elsevier.