Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by diminished degradation of the
glycosaminoglycans heparan sulfate (HS) and
dermatan sulfate (DS). Patients present with a variety of symptoms, including severe skeletal disease. Current therapeutic strategies have only limited effects on
bone disease. The
isoflavone genistein has been studied as a potential
therapy for the
mucopolysaccharidoses because of its putative ability to inhibit GAG synthesis and subsequent accumulation. Cell, animal, and clinical studies, however, showed variable outcomes. To determine the effects of
genistein on MPS I-related
bone disease, wild-type (WT) and MPS I mice were fed a
genistein-supplemented diet (corresponding to a dose of approximately 160 mg/kg/day) for 8 weeks. HS and DS levels in bone and plasma remained unchanged after
genistein supplementation, while liver HS levels were decreased in
genistein-fed MPS I mice as compared to untreated MPS I mice. Unexpectedly,
genistein-fed mice exhibited significantly decreased body length and femur length. In addition, 60% of
genistein-fed MPS I mice developed a scrotal
hernia and/or
scrotal hydrocele, manifestations, which were absent in WT or untreated MPS I mice. In contrast to studies in MPS III mice, our study in MPS I mice demonstraes no beneficial but even potential adverse effects of
genistein supplementation. Our results urge for a cautious approach on the use of
genistein, at least in patients with MPS I.