Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls

Abstract

Mucopolysaccharidosis II (MPS II), or Hunter syndrome, is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Affected patients suffer progressive damage to multiple organ systems and early mortality. Two thirds of patients also manifest cognitive impairment and developmental delays. MPS II can be extremely difficult to diagnose before irreversible organ and tissue damage has occurred because of an insidious onset and the overlap in signs and symptoms with common childhood complaints. This is particularly true of patients without cognitive impairment (attenuated phenotype). Although not curative, early treatment with enzyme replacement therapy before irreversible organ damage has occurred may result in the greatest clinical benefit. Here, the signs, symptoms, and surgical history that should trigger suspicion of MPS II are described, and the diagnostic process is reviewed with a focus on practical considerations and the avoidance of common diagnostic pitfalls. Once a diagnosis is made, multidisciplinary management with an extended team of pediatric specialists is essential and should involve the pediatrician or family practice physician as facilitator and medical home for the patient and family.

Conclusion: Because routine newborn screening is not yet available for MPS II, the involvement and awareness of pediatricians, family practice physicians, and pediatric specialists is critical for early identification, diagnosis, and referral in order to help optimize patient outcomes.

Fig. 1

Coarse facies in a 5-year-old child with MPS II. Note the frontal bossing, heavy eyebrows, puffy eyes, broad “saddle” nose, large jowls, thick lips, and enlarged tongue

Fig. 2

Patient D (attenuated phenotype) at 13 years of age. Note that the coarse facies are more subtle than seen in patients with the severe phenotype

Fig. 3

Skeletal manifestations of MPS II: a 33° scoliosis with coarseness of the bones and widening of the ribs in a 16-year-old patient with attenuated MPS II; b magnetic resonance imaging demonstrating mild thoracolumbar kyphosis and typical anterior vertebral body deficiency in a 16-year-old patient with attenuated MPS II; c significant thoracolumbar kyphosis in a 4-year-old patient with severe MPS II; d caput valgum and mild femoral head uncoverage in a 9-year-old patient with severe MPS II; e J-shaped sella in a 21-month-old patient with MPS II; f severe delay in maturation compatible with 3–6 months of age, mild proximal tapering of the metacarpals, and minimal slenderness of the distal phalanges in a 21-month-old patient with MPS II. Images a–d reproduced with permission from White et al. [45]

Fig. 4

Diagnostic algorithm for MPS II