Biochemical and molecular analysis in a patient with the severe form of Hunter syndrome after bone marrow transplantation

Am J Med Genet. 1996 Sep 6;64(4):531-5. doi: 10.1002/(SICI)1096-8628(19960906)64:4<531::AID-AJMG1>3.0.CO;2-S.


Hunter syndrome (mucopolysaccharidosis type II, or MPS II) results from a deficiency of iduronate-2-sulfatase (IDS) activity due to a primary genetic defect in the X-chromosomal iduronate-2-sulfatase gene. We have studied a 10-year-old male, diagnosed with Hunter syndrome at age 2 years, who underwent bone marrow transplantation (BMT) at age 5 years. To evaluate the metabolic effect of BMT, biochemical and enzymatic studies were performed. Urinary glycosaminoglycans (GAGs) were quantitated, and iduronate-2-sulfatase activity was measured in serum, leukocytes, and liver homogenates. Decreased urinary glycosaminoglycan excretion and increased iduronate-2-sulfatase activity in serum and leukocytes were observed. Furthermore, molecular analysis was performed using reverse transcriptional polymerase chain reaction (RT-PCR) sequencing and restriction enzyme assay. The patient was found to have a novel nonsense mutation, L279X (TTA to TGA) in exon 6 of the IDS gene, inherited from his mother. A comparison of the DNA contents of cultured skin fibroblasts prior to BMT with leukocyte DNA after BMT showed coexisting host mutant and donor normal alleles in post-BMT leukocyte DNA. We postulate that the L279X mutation is a severe disease-causing mutation for Hunter syndrome.

MeSH terms

  • Bone Marrow Transplantation*
  • Child
  • Humans
  • Male
  • Mucopolysaccharidosis II / genetics*
  • Pedigree
  • Polymerase Chain Reaction