X-linked spermine synthase gene (SMS) defect: The first polyamine deficiency syndrome

A. Lauren Cason, Yoshihiko Ikeguchi, Cindy Skinner, Tim C. Wood, Kenton R. Holden, Herbert A. Lubs, Francisco Martinez, Richard J. Simensen, Roger R. Stevenson, Anthony E. Pegg, Charles E. Schwartz

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Polyamines (putrescine, spermidine, spermine) are ubiquitous, simple molecules that interact with a variety of other molecules in the cell, including nucleic acids, phospholipids and proteins. Various studies indicate that polyamines are essential for normal cell growth and differentiation. Furthermore, these molecules, especially spermine, have been shown to modulate ion channel activities of certain cells. Nonetheless, little is known about the specific cellular functions of these compounds, and extensive laboratory investigations have failed to identify a heritable condition in humans in which polyamine synthesis is perturbed. We report the first polyamine deficiency syndrome caused by a defect in spermine synthase (SMS). The defect results from a splice mutation, and is associated with the Snyder-Robinson syndrome (SRS, OMIM9583), an X-linked mental retardation disorder. The affected males have mild-to-moderate mental retardation (MR), hypotonia, cerebellar circuitry dysfunction, facial asymmetry, thin habitus, osteoporosis, kyphoscoliosis, decreased activity of SMS, correspondingly low levels of intracellular spermine in lymphocytes and fibroblasts, and elevated spermidine/spermine ratios. The clinical features observed in SRS are consistent with cerebellar dysfunction and a defective functioning of red nucleus neurons, which, at least in rats, contain high levels of spermine. Additionally, the presence of MR reflects a role for spermine in cognitive function, possibly by spermine's ability to function as an 'intrinsic gateway' molecule for inward rectifier K+ channels.

Original languageEnglish (US)
Pages (from-to)937-944
Number of pages8
JournalEuropean Journal of Human Genetics
Issue number12
StatePublished - Dec 2003

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'X-linked spermine synthase gene (SMS) defect: The first polyamine deficiency syndrome'. Together they form a unique fingerprint.

Cite this