Treatment Enzyme replacement therapy (laronidase) is available. The enzyme is produced with recombinant technology and is successful where previous attempts with enzymes delivered by white cell or other infusions had been ineffective. Hematopoietic stem cell bone marrow transplantation (cord blood from unrelated donors) has also been used (see Staba et al). To be effective, treatment must commence before the accumulation of glycosaminoglycans and neurologic decline. The eye and bone deterioration associated with Hurler disease is not improved. In children with the milder Scheie form and those with CNS involvement, bone marrow transplantation is not helpful and enzyme replacement is recommended. Enzyme treatment is also being tried concurrently with bone marrow transplantation in early cases. These approaches have not been effective in the Hunter or the Sanfilippo diseases, discussed below.
Hunter Disease (MPS II, IDS Mutation)
Unlike the Hurler and other types, the Hunter form (MPS II) is transmitted as an X-linked trait. The Hurler and Hunter syndromes are clinically alike except that the Hunter form is milder: developmental delay is less severe than in the Hurler type, deafness is less common, and corneal clouding is usually absent. Probably there are two forms of the syndrome—a more severe one, in which the patients do not survive beyond their midteens, and a less severe form with relatively normal intelligence and survival to middle age. Excessive amounts of dermatan and heparan sulfate are excreted in the urine. The basic abnormality is a deficiency of iduronate sulfatase. The enzyme replacement therapy, idursulfase, administered weekly, intravenously may delay some of the features of the disorder.
Sanfilippo Disease (MPS III, Several Genes Implicated)
This form, or MPS III, expresses itself clinically between 2 and 3 years of age, with progressive intellectual deterioration. The patients are of short stature, but in other respects the physical changes are fewer and less severe than in the Hunter and Hurler syndromes. Four types of Sanfilippo disease, designated A, B, C, and D, are distinguished on the basis of their enzymatic defects. All subtypes are phenotypically similar, and all of them may excrete excessive amounts of heparan sulfate in the urine.
Morquio Disease (MPS IV, GALNS and GLB1 Mutations)
This form of the disease, MPS IV, is characterized by marked dwarfism and osteoporosis. Skeletal deformity and compression of the spinal cord and medulla are constant threats because of hypoplasia of the odontoid process and atlantoaxial dislocation and thickening of the dura around the cervical cord and inferior surface of the cerebellum. Intelligence is affected only slightly or not at all. Corneal opacities may be present. Patients excrete large amounts of keratan sulfate in the urine; two types of enzymatic deficiencies have been identified. Replacement with elosulfase has been partially effective and stem cell transplantation and gene therapy are being investigated.
Maroteaux-Lamy Disease (MPS VI, ARSB Mutation)
This syndrome, MPS VI, includes severe skeletal deformities (short stature, anteriorly beaked vertebrae) but normal intelligence. Several patients observed by our colleagues have had a cervical pachymeningitis with spinal cord compression and hydrocephalus during adult life. Spinal cord function improved with cervical decompression and the hydrocephalus with ventriculoatrial shunting (Young et al). Hepatosplenomegaly is often present. Large amounts of dermatan sulfate are excreted in the urine, as a result of an arylsulfatase B deficiency. Enzyme replacement with galsulfase has been implemented.
β-Glucuronidase Deficiency (Sly Disease, MPS VII,