6.2.10.2  MPS II: Hunter Syndrome

In the Hunter syndrome (MPS II), the metabolic defect is a deficiency of the lysosomal enzyme iduronate- 2-­sulfatase. There is urinary excretion of both dermatan sulfate and heparan. In contrast to the other mucopolysaccharidoses, MPS II is X-linked recessive. Phenotypically­ the Hunter syndrome closely resembles the Hurler prototype. The manifestations of MPS II, however, are generally less severe than those of MPS I H, and the Hunter syndrome is distinguished clinically by longer survival and by the absence of gross corneal clouding.

In the Hunter syndrome the facial features are coarse, the supraorbital ridges tend to be prominent, the tongue is large, and the teeth are widely spaced. Dwarfing and stiffness of the joints are prominent features. Clawhand deformity is common. As a rule there is hepatosplenomegaly. The abdomen is protuberant. Hernias are common. Cardiac involvement is a regular feature of the syndrome; congestive heart failure and coronary artery disease are major causes of death. Respiratory disability also is evident in most patients. Neurologic manifestations vary. Spastic quadriplegia may develop from impingement on the cervical spinal cord. Hydrocephalus may develop. Mental deterioration occurs, but the severity and the rate of regression vary. Progressive deafness occurs in most patients.

A distinctive feature of the Hunter syndrome is the occurrence of nodular or pebbly ivory-colored skin lesions, most frequently on the back extending from the inferior angle of the scapula toward the axillary line, less often in the pectoral area, nape of the neck, and lateral aspect of the upper arms and thighs.

In contrast to MPS I H, obvious corneal clouding is not a regular feature of MPS II. However, slight corneal changes may be detected by slit-lamp examination in older patients with Hunter syndrome, and histologic evidence of corneal mucopolysaccharide accumulation has been reported.

The principal ophthalmologic manifestation of MPS II is progressive retinal degeneration with attendant impairment of vision. Night vision problems and visual field defects are common. The disorder may lead to blindness. The fundus signs include retinal pigmentary changes, sometimes spicule formation, retinal arteriolar attenuation, and optic disc pallor. The ERG is usually reduced or extinguished.

The Sanfilippo syndrome (MPS III), sometimes referred to as polydystrophic oligophrenia, is a mucopolysaccharidosis in which there is severe mental retardation and relatively less severe somatic abnormalities. Four biochemically different, clinically similar forms of the syndrome occur. Each type involves an enzyme responsible for a separate step in the sequential degradation of heparan sulfate. Mental retardation, the predominant clinical manifestation of MPS III, usually becomes evident in the first few years of life. With increasing age there is progressive deterioration of intellect and behavior.

Somatic abnormalities typical of the mucopolysaccharidoses tend to be mild or inconspicuous. There is some coarseness of facial features. Generalized hirsutism may be marked. Dwarfing, joint stiffness, and clawhand deformity are usually evident but are not as severe as in the Hurler prototype. Slight to moderate hepatosplenomegaly develops, and the abdomen tends to be protuberant. Respiratory difficulties are common. Heart involvement may occur but tends to be less severe than in other mucopolysaccharidoses.

Ocular manifestations are mild if present at all. Corneal clouding does not occur in MPS III, although microscopic changes were noted in one of Sanfilippo’s patients. Some retinal involvement may occur in MPS III. Narrowing of the retinal vessels and pigmentary changes have been noted. Subnormal ERG responses have been recorded. Optic atrophy may develop.

6.2.10.4  MPS IV: Morquio Syndrome

Morquio syndrome is characterized by severe dwarfism and skeletal deformity, often with neurologic complications, and a number of extraskeletal abnormalities such as corneal clouding and cardiac valvular disease. In MPS IV, there is defective degradation of keratan sulfate. There is excessive urinary excretion of keratan sulfate, although the amount of keratan sulfate in the urine tends to diminish as affected patients grow older.

As with Sanfilippo syndrome, clinically similar but enzymatically different forms of Morquio syndrome occur.

Patients with Morquio syndrome appear normal in the first months of life, although radiographic signs may be present early. With growth during the first years of life, abnormalities such as retarded growth,­knock-knees,