Hunter Syndrome, MPS II


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Introduction to Hunter Syndrome

Hunter syndrome is an X-linked recessive disorder that belongs to a family of disorders identified as lysosomal storage diseases, and historically as one of the mucopolysaccharidoses. This disorder is characterized by the lysosomal accumulation of dermatan and heparan sulfates as a consequence of deficiencies in the lysosomal hydrolase iduronate sulfatase. Iduronate sulfatase is a member of a family of sulfatases, many of which are necessary for the degradation of the glycosaminoglycans (e.g. see the Mucoploysaccharidoses page). Iduronate sulfatase (also called iduronate 2-sulfatase) hydrolyzes sulfates from the 2- position of L-iduronate present in dermatan and heparan sulfates. The enzyme was originally referred to as the "Hunter corrective factor". Hunter syndrome is the only mucopolysaccharidoses that is X-linked.

The iduronate sulfatase gene (IDS) is located on the X chromosome at Xq28 spanning 24 kb and encompassing 11 exons that generate three alternatively spliced mRNAs encoding three isoforms (a, b, and c). Removal of the 25 amino acid signal sequence generates the proprotein and finally, an additional 8 amino acids are removed from the N-terminus of the proprotein generating the functional glycoprotein. Numerous mutations and deletions have been identified in the IDS gene resulting in Hunter syndrome. The majority of Hunter syndrome mutations are missense, nonsense, and frameshift mutations with several small deletions or insertions as well. All patients harboring mutations caused by large deletions or rearrangements in the IDS gene manifest with the severe forms of Hunter syndrome.

Clinical Features of Hunter Syndrome

Clinically, Hunter syndrome is divided into severe and mild classifications. The clinical presentation of the severe form of Hunter syndrome has many similarities to those seen in Hurler syndrome without the corneal clouding. In addition, the symptoms of Hunter progress slower than those of Hurler syndrome. The mild form of Hunter syndrome is similar to the Hurler-Scheie syndrome and Scheie syndrome. Hunter syndrome is inherited as an X-linked recessive disorder and affected males do not reproduce. This latter fact precludes the presentation of affected females.

Patients with the severe form of Hunter syndrome present with characteristic clinical features. These include short stature, skeletal deformities, joint stiffness, coarse facial features and mental retardation. Onset of symptoms of the severe form are usually seen between 2 and 4 years of age. As a consequence of autonomic nervous system involvement many patients suffer from chronic diarrhea. Extensive neurological degeneration precedes death in patients with the severe form of Hunter syndrome with death occurring between 10 and 15 years of age.

Patients with the mild form of Hunter syndrome generally have normal intelligence and survive into adulthood. Some of the symptoms in mild form patients can be as severe as those in the severe form but the progression of deterioration is much slower. Although some patients with the mild form of Hunters can survive into their 50's or 60's death often occurs in early adulthood as a consequence of cardiac failure and pulmonary obstruction.

 

 

 

 

 

 

 

 

 

 

 


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Last modified: June 2, 2015