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Denouement and Discussion: Hunter Syndrome (Mucopolysaccharidosis IIA)
Figure 1. The head is dolichocephalic in shape with coarse facial features.
Figure 2. Claw hands and flexion contractures of the elbows are present.
Figure 3. Ivory-colored papules are present over the chest and upper arm.
Hunter syndrome is a rare (1 per 130,000 live-born males) X-linked, recessive disorder characterized by a deficiency of iduronate sulfatase. The enzyme deficiency results in the deposition and accumulation of the mucopolysaccharides dermatan and heparan sulfate in the brain and other tissues.1 Two clinical varieties of Hunter syndrome are recognized: mucopolysaccharidosis (MPS) IIA, resulting in severely affected males, and MPS IIB, a mild form of the disorder.2
In MPS IIA, affected males demonstrate progressive physical and mental abnormalities by age 2 years, including progressive mental retardation, short stature, joint contractures, coarse facial features, hypertrichosis, prominent forehead and dolichocephaly, and thickening of the skin.
Additional features of the disorder include progressive deafness, macroglossia, dental deformities, and hernias. Thickening of the valve leaflets may result in the appearance of cardiac murmurs, ventricular enlargement, congestive heart failure, and arrhythmias. Visual loss may result from papilledema secondary to increased intracranial pressure from hydrocephalus. In addition to thickened skin, firm, ivory or skin-colored papules and nodules filled with acidic glycosaminoglycans may appear, often in reticular patterns over the chest, upper arms, and thighs.
As the deposition of mucopolysaccharides continues, affected males demonstrate progressive mental deterioration and aggressive, hyperactive behavior. In MPS IIB, somatic manifestations, although similar to MPS IIA, develop more slowly. Joint contractures and carpal tunnel syndrome may develop in adulthood and occasionally in childhood. Intelligence is normal, however.
Prognosis and molecular basis
The health of boys affected with MPS IIA progressively deteriorates, usually resulting in death between age 10 and 15 years.3 In MPS IIB, the milder variant of this disorder, survival into the fifth and sixth decades is not unusual.3
The gene for Hunter syndrome has been mapped to the Xq27/Xq28 region, distal to the fragile X mutation (FRAXA).4 The spectrum of severity of the disorder has been attributed to different mutations of the gene responsible, ranging from full deletions in more severely affected individuals to partial deletions or other gross rearrangements in those with milder phenotypes.5
Diagnosis and treatment
The diagnosis of Hunter syndrome is made by demonstrating deficiency of the enzyme iduronate sulfatase in serum, white blood cells, or fibroblasts. The carrier status of females may be ascertained through linkage analysis studies or by measuring iduronate sulfatase activity in serum, leukocyte homogenates, or fibroblasts.6,7 Prenatal diagnosis by enzyme assay of amniotic cells or chorionic biopsies have also been used.8
The treatment of severe Hunter syndrome is mainly supportive. Bone marrow transplantation and gene therapy to halt progressive neurological and physical deterioration have been attempted, but results thus far have been disappointing.9,10
Hunter syndrome is most commonly confused with other types of MPS, particularly Hurler and Hurler-Scheie syndromes. In these disorders corneal clouding is a major feature, and skin papules do not occur. In addition, Hunter syndrome is the only MPS that is X-linked. The mucolipidoses may have similar phenotypic features. The flesh- to ivory-colored skin papules are quite characteristic of Hunter syndrome and seen in both variants. The papules offer a cutaneous diagnostic marker of the disorder.
Picture of the Month. Arch Pediatr Adolesc Med. 2000;154(1):86. doi:
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