Hunter syndrome

The mucopolysaccharidoses share a common mechanism of causation, as illustrated in Figure 48-10. They are inherited in an autosomal recessive manner, with Hurler and Hunter syndromes being perhaps the most widely studied. None are common. In some cases, a family history of a mucopolysaccharidosis is obtained. Specific laboratory investigations of help in their diagnosis are urine testing for the presence of increased... 

Hunter syndrome (MPS-II) is an X-linked disorder arising from deficiency of iduronate sulfatase,... 

Idursulfase (Elaprase) is a drug used to treat mucopolysaccharidosis II or Hunter syndrome. It is a lysosomal storage disease caused by iduronate-2-sulfatase deficiency. Idursulfase is a purified form of iduronate-2-sulfatase produced by recombinant DNA technology in a human cell line. The drug provides clinically important benefits to Hunter syndrome patients. After intravenous infusion Idursulfase is eliminated by peptide hydrolysis with an elimination half-life of 45 minutes. The most common adverse events are hypersensitivity reactions, pyrexia, headache and arthralgia. 

This "Hurler corrective factor" was identified as an a-L-iduronidase. In the Hunter syndrome (MPS II) dermatan sulfate and heparan sulfate accumulate. 

Immunodeficiency, X-linked r with hyper IgM Lymphoproliterative syndrome s Hemophilia B t Albinism-deafness syndrome u Fragile X syndrome Hunter syndrome Hemophilia A... 

The deficiency of any lysosomal enzyme results in accumulation of its substrate in lysosomes. Some of these diseases include Hurler syndrome, Hunter syndrome, I-cell disease, Niemann-Pick disease,... 

Muenzer, J., Lamsa, J. C., Garcia, A., Dacosta, J., Garcia, J. and Treco, D. A. (2002). Enzyme replacement therapy in mucopolysaccharidosis type II (Hunter syndrome) A preliminary report. Acta Paediatr. Suppl. 91, 98-99. 

Tomanin, R., Friso, A., Alba, S., Piller, P. E., Mennuni, C., La Monica, N., Hortelano, G., Zacchello, F. and Scarpa, M. (2002). Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome). Acta Paediatr. 91 (Suppl.), 100-104. 

Bondeson ML, Dahl N, Malmgren H, Kleijer WJ, Tonnesen T, Carlberg BM, Pettersson U. Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome. Hum Mol Genet 1995 4(4) 615-621. 

Mucopolysaccharidosis II (Hunter Syndrome) Iduronate 2-sulphatase HS, DS Short stature, skeletal dysplasia, coarse facial features, joint stiffness, visceromegaly, cardiac disease, comeal clouding, CNS involvement... 

Indications Hunter syndrome, Mucopolysaccharidosis II Category Enzyme Half-life 46 minutes... 

Cardone M, Polito VA, Pepe S, Mann L, D Azzo A, Auricchio A, Ballabio A, Cosma MP. Correction of Hunter syndrome in the MPSII mouse model by AAV2/8-mediated gene delivery. Hum Mol Genet 2006 15 1225-1236. 

Dean MF, Muir H, Benson PF, et al. Increased breakdown of glycosaminoglycans and appearance of corrective enzyme after skin transplants in Hunter syndrome. Nature 1975 257 609- 614. 

Other causes Hunter syndrome, Hurler syndrome, or Morquio syndrome... 

Excessive accumulation of proteins, nucleic acids, carbohydrates, and lipids can result from deficiency of one or more lysosomal hydrolases. Lysosomal storage diseases are classified by the stored material. Accumulation of gly-cosaminoglycans results in mucopolysaccharidoses. Common causes of this disorder include Hunter syndrome, Hurler syndrome, and Sanfihppo syndrome. Sanfdippo syndrome is inherited in an autosomal recessive pattern and clinically evident by profound mental retardation, lack of normal developmental milestones, and significant language delay. Sanfdippo syndrome results in an excess of heparan sulfate and can be caused by a variety of enzyme deficiencies. 

The mucopolysaccharidoses are classified into seven clinical types and all are transmitted by autosomal recessive inheritance except for Hunter syndrome (MPS II, iduronate sulfatase deficiency), which is an X-linked disorder. Diagnosis of the specific disorder is made by measuring the specific enzyme activities in leukocytes or cultured skin fibroblasts. Because it takes some time... 

A 3-year-old male with coarse facial features, progressive loss of motor skills, hepatosplenomegaly and chronic diarrhea is suspected of having Hunter syndrome (MPS II). Which of the following monosaccharide residues would be expected to be found at the nom-educing end of glycosaminoglycans in this patient s urine ... 

B. All of the mucopolysaccharidoses are transmitted by autosomal recessive inheritance except Hunter syndrome (MPS II), a deficiency in iduronate sulfatase that is X-linked recessive. Since Hunter syndrome is X-linked, it is almost exclusively seen in males. Since our patient is female, she would not be expected to have an X-linked disorder. 

E. Since this patient is suspected of having Hunter syndrome, a deficiency in iduronate sulfatase, iduronate 2-sulfate would be expected to be present at the nonreducing end of glycosaminoglycans found in this patient s urine. A deficiency of iduronate sulfatase would prevent the sulfate ester bond of iduronate 2-sulfate residues from being hydrolyzed and further degradation of the glycosaminoglycan would be halted. 

Liebaers, I., and Neufeld, E. F., Iduronate sulfatase activity in serum, lymphocytes and fibroblasts—simplified diagnosis of the Hunter syndrome. Pediatr. Res. 10, 733-736 (1976). 

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