Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (429 page)

Suggested Reading

Suzuki Y, Oshima A, Nanba E. Beta-galactosidase deficiency (beta-galactosidosis): GM1 gangliosidosis and Morquio B disease. In: Scriver CR, Beaudet AL, Sly WS, et al., eds.
The Metabolic and Molecular Bases of Inherited Disease
.
Vol. II
. 8th ed. New York: McGraw-Hill; 2001:3775–3809.

HUNTER SYNDROME (MUCOPOLYSACCHARIDOSIS II; IDURONATE-2-SULFATASE DEFICIENCY)

MIM #309900

   Definition

Mucopolysaccharidosis II arises from iduronate-2-sulfatase (I2S) deficiency, which results in tissue deposits of mucopolysaccharides and urinary excretion of large amounts of chondroitin sulfate B and heparitin sulfate. This sex-linked type of mucopolysaccharidosis differs from mucopolysaccharidosis I in being on the average less severe and in not showing corneal clouding. Features are dysostosis with dwarfism, grotesque facies, hepatosplenomegaly from mucopolysaccharide deposits, cardiovascular disorders from mucopolysaccharide deposits in the intima, deafness, and excretion of large amounts of chondroitin sulfate B and heparitin sulfate in the urine.

   Relevant Tests and Diagnostic Value

   Quantitation of total glucosaminoglycans in urine and accumulation of keratan sulfate in tissues

   Definitive diagnosis is established by iduronate-2-sulfatase enzyme assay in cultured fibroblasts, leukocytes, amniocytes, or chorionic villi

   Sequence analysis of the iduronate-2-sulfatase gene

   Other Considerations

Hunter syndrome is clinically similar to Hurler syndrome but milder, with no corneal opacity. Maternal serum shows increased activity of iduronate sulfate sulfatase with a normal or heterozygous fetus but no increase if fetus has Hunter syndrome.

Suggested Reading

Jonsson JJ, Aronovich EL, Braun SE, et al. Molecular diagnosis of mucopolysaccharidosis type II (Hunter syndrome) by automated sequencing and computer-assisted interpretation: toward mutation mapping of the iduronate-2-sulfatase gene.
Am J Hum Genet.
1995;56:597–607.

HURLER SYNDROME (MUCOPOLYSACCHARIDOSIS 1H, MPS1-H)

MIM #607014

   Definition

Hurler syndrome is an autosomal inherited disorder caused by mutations in the gene encoding alpha-
L
-iduronidase (IDUA) at 4p16.3 that hydrolyzes the terminal alpha-
L
-iduronic acid residues of the glycosaminoglycans dermatan sulfate and heparan sulfate. The accumulation of partially degraded glycosaminoglycans interferes with cell, tissue, and organ function.

   Who Should Be Suspected?

Deficiency of alpha-
L
-iduronidase can result in a wide range of phenotypic involvement with three major recognized clinical entities: Hurler (mucopolysaccharidosis IH), Scheie (mucopolysaccharidosis IS), and Hurler-Scheie (mucopolysaccharidosis IH/S) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the mucopolysaccharidosis I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression.

   Relevant Tests and Diagnostic Value

   Urinary excretion of glycosaminoglycans.

   Definitive diagnosis is established by alpha-
L
-iduronidase enzyme assay using artificial substrates (fluorogenic or chromogenic) in cultured fibroblasts, leukocytes, amniocytes, or chorionic villi.