Next Article in Journal
New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins
Previous Article in Journal
Report from the Scientific Poster Session at the 13th Annual Cardiometabolic Health Congress in Boston, USA, 24–27 October 2018
Previous Article in Special Issue
Antizyme Inhibitors in Polyamine Metabolism and Beyond: Physiopathological Implications
Article Menu
Issue 4 (December) cover image

Export Article

Open AccessFeature PaperArticle
Med. Sci. 2018, 6(4), 112;

Polyamine Homeostasis in Snyder-Robinson Syndrome

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA
The Greenwood Genetic Center, Greenwood, SC 29646, USA
Author to whom correspondence should be addressed.
Received: 15 November 2018 / Revised: 29 November 2018 / Accepted: 3 December 2018 / Published: 7 December 2018
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
Full-Text   |   PDF [1947 KB, uploaded 10 December 2018]   |  
  |   Review Reports


Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome. View Full-Text
Keywords: Snyder-Robinson Syndrome; spermine synthase; X-linked intellectual disability; polyamine transport; spermidine; spermine; transglutaminase Snyder-Robinson Syndrome; spermine synthase; X-linked intellectual disability; polyamine transport; spermidine; spermine; transglutaminase

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Murray-Stewart, T.; Dunworth, M.; Foley, J.R.; Schwartz, C.E.; Casero, R.A., Jr. Polyamine Homeostasis in Snyder-Robinson Syndrome. Med. Sci. 2018, 6, 112.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Med. Sci. EISSN 2076-3271 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top