Rebalancing polyamine levels to treat Snyder–Robinson syndrome

• Published in: EMBO molecular medicine Vol. 15; no. 11; pp. e18506 - 3
• Main Author: Gilmour, Susan K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-11-2023; EMBO Press; John Wiley and Sons Inc; Springer Nature
• Subjects: Biomedicine; Biosynthesis; Cell growth; Children; EMBO16; EMBO21; Genetic disorders; Intellectual disabilities; Kyphosis; Metabolism; Metabolites; Molecular Medicine; Mutation; Nervous system; Neurological disorders; News & Views; Osteoporosis; Patients; Polyamines; Ratios; Scoliosis; Seizures; Sex linkage; Spermine; Spermine synthase; Symptom management; Views
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.15252/emmm.202318506

Snyder–Robinson syndrome (SRS) is a rare genetic disorder characterized by intellectual disability and delayed development beginning early in childhood. It was first described in a single family in 1969 as a sex‐linked disorder (Snyder & Robinson, 1969) and has since been only identified in less than 100 individuals worldwide. Inherited in an X‐linked recessive pattern, SRS has only been identified in males thus far. Snyder–Robinson syndrome primarily affects the nervous system and skeletal tissues and is caused by loss‐of‐function mutations in the gene encoding spermine synthase (SMS), a polyamine biosynthesis enzyme. Affected males display a collection of clinical features including intellectual disability ranging from mild to profound, speech and vision impairment, osteoporosis, hypotonia, and increasing loss of muscle tissue with age, kyphoscoliosis, seizures, and distinctive facial features including a prominent lower lip and facial asymmetry. Currently, there is no cure or treatment for this debilitating disorder aside from symptom management.
Graphical Abstract
S. Gilmour
discusses the study by Stewart
et al
, in this issue of
EMBO Mol Med
, that proposes the use of 2‐difluoromethylornithine (DFMO) to rebalance the relative levels of the polyamines spermidine and spermine in order to treat Snyder–Robinson syndrome patients.