Impaired osteoblast and osteoclast function characterize the osteoporosis of Snyder - Robinson syndrome.

Mark McIntosh,'s picture
PubMed URL: 
http://www.ncbi.nlm.nih.gov/pubmed/25888122
Author: 
Boerkoel CF
Author List: 
Albert JS
Bhattacharyya N
Wolfe LA
Bone WP
Maduro V
Accardi J
Adams DR
Schwartz CE
Norris J
Wood T
Gafni RI
Collins MT
Tosi LL
Markello TC
Gahl WA
Boerkoel CF
Journal: 
Orphanet J Rare Dis
PubMed ID: 
25888122
Pagination: 
27
Volume: 
10
Abstract: 
Snyder-Robinson Syndrome (SRS) is an X-linked intellectual disability disorder also characterized by osteoporosis, scoliosis, and dysmorphic facial features. It is caused by mutations in SMS, a ubiquitously expressed gene encoding the polyamine biosynthetic enzyme spermine synthase. We hypothesized that the tissue specificity of SRS arises from differential sensitivity to spermidine toxicity or spermine deficiency.We performed detailed clinical, endocrine, histopathologic, and morphometric studies on two affected brothers with a spermine synthase loss of function mutation (NM_004595.4:c.443A > G, p.Gln148Arg). We also measured spermine and spermidine levels in cultured human bone marrow stromal cells (hBMSCs) and fibroblasts using the Biochrom 30 polyamine protocol and assessed the osteogenic potential of hBMSCs.In addition to the known tissue-specific features of SRS, the propositi manifested retinal pigmentary changes, recurrent episodes of hyper- and hypoglycemia, nephrocalcinosis, renal cysts, and frequent respiratory infections. Bone histopathology and morphometry identified a profound depletion of osteoblasts and osteoclasts, absence of a trabecular meshwork, a low bone volume and a thin cortex. Comparison of cultured fibroblasts from affected and unaffected individuals showed relatively small changes in polyamine content, whereas comparison of cultured osteoblasts identified marked differences in spermidine and spermine content. Osteogenic differentiation of the SRS-derived hBMSCs identified a severe deficiency of calcium phosphate mineralization.Our findings support the hypothesis that cell specific alterations in polyamine metabolism contribute to the tissue specificity of SRS features, and that the low bone density arises from a failure of mineralization.
Published Date: 
January, 2015

Appointments & Referrals

FIND A SPECIALIST

Publications

Read inspiring stories, news and updates about the Institute's patient care, research, special education, professional training, and community programs.

 

Resource Finder

 

A free resource that provides access to information and support for individuals and families living with developmental disabilities.