INTRODUCTION	Section 2 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Background: The mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders caused by the deficiency of specific enzymes that are required for the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The inability to degrade these macromolecules, which are ubiquitous, results in their storage in a variety of tissues, including liver, spleen, heart, connective tissue, and others. The precise clinical features of each MPS depend upon the specific enzymatic deficiency and the pattern of storage of the particular MPS. Thus, these disorders display extensive genetic heterogeneity. In addition to somatic features, which may be severe, mental retardation also occurs in MPS-IH, MPS-II and MPSIII. Although the MPSs are rare individually, the overall incidence is approximately 1 in 25,000 people.

The diagnosis of a MPS is by determination of the specific enzymatic activity in cultured fibroblasts, leukocytes, or serum. Prenatal diagnosis by measurement of the particular enzyme in cultured amniocytes or chorionic villi is also possible.

	CLINICAL	Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History: As the name Hurler-Scheie syndrome suggests, the clinical features of type I H/S lie somewhat between those of Hurler syndrome and Scheie syndrome. Until a patient's specific molecular defect is determined, assignment to types IH, IS, or I H/S is based on the severity of the symptoms. Progressive involvement of the various organs and tissues of the body occurs in all 3 subgroups of type I MPS.

In general, type I H/S symptom onset occurs in patients older than those typically affected by type IH. Symptom onset, however, varies considerably both within and among the 3 subgroups. Diagnoses based solely on the onset of clinical symptoms may be proven incorrect by subsequent precise determination of the mutant alleles involved. In each of the 3 major groups of MPS I, children are usually born without distinguishing clinical features. In patients with type IH, craniofacial abnormalities usually develop by age 1-2 years; in type I H/S, by age 3-8 years; and in type IS, at age 5 or by age 10-20 years.

Patients with type I H/S usually have normal intelligence, although, in 1976, Winters et al described an interesting case of type I MPS that differed from types IH and IS. The patient, who might have had type I H/S, was aged 10 years before problems were noted in school. She did not develop coarse facial features until age 20 years, and she died at age 25 years.

Features observed in type IH, such as joint stiffness, corneal clouding, and valvular heart disease, may also occur in patients with type I H/S but usually not until they become teenagers.

Physical: MPS type I H/S is intermediate in severity compared to type IS and type IH.

Intelligence is normal, with physical symptoms that are not as severe as those observed in Hurlers syndrome.

All symptoms develop in the early-to-late teens and include valvular heart disease, corneal clouding, deafness, and joint stiffness.

Causes:

• A deficiency of the lysosomal enzyme, a-L-iduronidase

• Accumulation of the undegraded mucopolysaccharides DS and HS in tissues and organs

• Storage of excess mucopolysaccharides, leading to numerous morphological abnormalities

• The metabolic defect in type I H/S has an autosomal recessive mode of inheritance. This mode is shared by all other MPS types except type II, which is transmitted as a sex-linked recessive defect.

• Both types IS and IH involve deficiencies of the a-L-iduronidase enzyme, which results from mutations at the same genetic locus. Because both occur at the same locus, genetic compounds of the 2 alleles are possible, and the compound produces type I H/S.

• The a-L-iduronidase gene has been mapped to chromosome band 4p16.3.