Genetic and Phenotypic Features of the Five Known Polyaminopathies: A Critical Narrative Review

Polyaminopathies are a recently described family of rare genetic neurodevelopmental disorders. Polyaminopathies disrupt the biosynthesis of the primary polyamines: putrescine, spermidine, and spermine. Snyder-Robinson syndrome results from hemizygous loss-of-function variants in the spermine synthase (SMS) gene, resulting in decreased or complete loss of spermine synthase enzyme activity. Bachmann-Bupp syndrome results from heterozygous gain-of-function variants in the ornithine decarboxylase 1 (ODC1) gene, resulting in increased ornithine decarboxylase enzyme activity. Faundes-Banka syndrome results from heterozygous loss-of-function variants in the eukaryotic translation initiation factor 5A (EIF5A) gene, impairing eIF5A protein function. DHPS (deoxyhypusine synthase) deficiency is an autosomal recessive disease and results from bi-allelic hypomorphic variants in the deoxyhypusine synthase (DHPS) gene, which results in reduced deoxyhypusine synthase enzyme activity. Finally, DOHH (deoxyhypusine hydroxylase) disorder is an autosomal recessive disorder caused by bi-allelic loss-of-function variants in the deoxyhypusine hydroxylase (DOHH) gene, which causes decreased deoxyhypusine hydroxylase enzyme activity. Snyder-Robinson syndrome was first described in 1969, while the other four syndromes have only been identified in the past 7 years. A comprehensive phenotypic and genotypic description of these five syndromes is needed. We review the clinical and genetic features of these five polyaminopathies to create an inclusive clinical resource. A systematic keyword search strategy was used to identify all published cases in PubMed, Web of Science, and Scopus databases. The five known syndromes associated with the polyamine pathway share many similar clinical phenotypes, and yet patients with each syndrome present with distinctive syndromic features. This review will serve as a valuable resource for clinicians diagnosing and caring for patients with these rare polyaminopathies.

Authors

Institutions

Publication Details

Journal
American Journal of Medical Genetics Part A
Published
2025-12-18
DOI
https://doi.org/10.1002/ajmga.70029
Primary Topic
Polyamine Metabolism and Applications
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Genetic and Phenotypic Features of the Five Known Polyaminopathies: A Critical Narrative Review

Orrin Devinsky, Colleen Olson, Sara M. Sarasua, Caleb Bupp et al.
American Journal of Medical Genetics Part A
Polyamine Metabolism and Applications
article

Genetic and Phenotypic Features of the Five Known Polyaminopathies: A Critical Narrative Review

Orrin Devinsky, Colleen Olson, Sara M. Sarasua, Caleb Bupp, Mary Jo Kutler, Elizabeth VanSickle, Katharina Steindl, Luigi Boccuto, André S. Bachmann, Julianne Michael, Angela Peron, Floris C. Hofstede, Mythily Ganapathi, Susan K. Gilmour, Tracy Lowe, Clément Prouteau, Alban Ziegler, Teresa L. Mastracci, Surender Rajasekaran, Víctor Faúndes, Christopher Farrell, Charles E. Schwartz, Tracy Murray Stewart, Robert A. Casero, Teri L. Koerner, Wendy K. Chung, Anthony E. Pegg
article en

Abstract

Polyaminopathies are a recently described family of rare genetic neurodevelopmental disorders. Polyaminopathies disrupt the biosynthesis of the primary polyamines: putrescine, spermidine, and spermine. Snyder-Robinson syndrome results from hemizygous loss-of-function variants in the spermine synthase (SMS) gene, resulting in decreased or complete loss of spermine synthase enzyme activity. Bachmann-Bupp syndrome results from heterozygous gain-of-function variants in the ornithine decarboxylase 1 (ODC1) gene, resulting in increased ornithine decarboxylase enzyme activity. Faundes-Banka syndrome results from heterozygous loss-of-function variants in the eukaryotic translation initiation factor 5A (EIF5A) gene, impairing eIF5A protein function. DHPS (deoxyhypusine synthase) deficiency is an autosomal recessive disease and results from bi-allelic hypomorphic variants in the deoxyhypusine synthase (DHPS) gene, which results in reduced deoxyhypusine synthase enzyme activity. Finally, DOHH (deoxyhypusine hydroxylase) disorder is an autosomal recessive disorder caused by bi-allelic loss-of-function variants in the deoxyhypusine hydroxylase (DOHH) gene, which causes decreased deoxyhypusine hydroxylase enzyme activity. Snyder-Robinson syndrome was first described in 1969, while the other four syndromes have only been identified in the past 7 years. A comprehensive phenotypic and genotypic description of these five syndromes is needed. We review the clinical and genetic features of these five polyaminopathies to create an inclusive clinical resource. A systematic keyword search strategy was used to identify all published cases in PubMed, Web of Science, and Scopus databases. The five known syndromes associated with the polyamine pathway share many similar clinical phenotypes, and yet patients with each syndrome present with distinctive syndromic features. This review will serve as a valuable resource for clinicians diagnosing and caring for patients with these rare polyaminopathies.

American Journal of Medical Genetics Part A
Universidad de Santiago de Chile (CL), Grand Rapids Community College (US), Boston Children's Hospital (US), Harvard University (US), Johns Hopkins University (US), Université Fédérale de Toulouse Midi-Pyrénées (FR), Lankenau Institute for Medical Research (US), University of Zurich (CH), Columbia University Irving Medical Center (US), University Medical Center Utrecht (NL), Lawton Public Schools (US), Meyer Children's Hospital (IT), Helen DeVos Children's Hospital (US), Parkinson's Foundation (US), Université d'Angers (FR), Indiana University – Purdue University Indianapolis (US), New York University (US), Clemson University (US), Penn State Milton S. Hershey Medical Center (US), Michigan State University (US)
Openalex Percentile: Top 63%
Polyamine Metabolism and Applications
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.