Harmonizing gene nomenclature and disease classification for ADSS1 myopathy
8 affiliations
- 1Inherited and Acquired Myopathies Program, Institute of Health and Sport, Victoria University, Melbourne, VIC Australia
- 2Melbourne Medical School – Western Health, Department of Medicine, University of Melbourne, Melbourne, VIC Australia
- 3Cure ADSSL1, Glendale, CA USA
- 4Purine and Pyrimidine Metabolism Unit, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
- 5Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA USA
- 6Faculty of Medicine, Department of Pediatric Metabolism, Ankara University, Ankara, Türkiye
- 7Ankara University Rare Diseases Application and Research Center, Ankara, Türkiye
- 8Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA USA
Abstract
ADSS1 myopathy is an ultra-rare autosomal recessive neuromuscular disorder caused by biallelic pathogenic variants in ADSS1 encoding the striated muscle isozyme of adenylosuccinate synthase involved in purine metabolism. Despite advances in clinical, genetic and mechanistic understanding, the condition remains inconsistently represented across clinical, genomic and registry systems. It is variably labelled as ADSSL1-related distal myopathy, nemaline myopathy, or more recently, a metabolic myopathy reflecting an inborn error of metabolism. These inconsistencies have practical consequences. Gene nomenclature and annotation drift introduces avoidable errors in variant interpretation, panel design and data integration, while imprecise disease classification based on early observations reduces clinical ascertainment of new cases, degrades longitudinal natural history studies, and delays clinical trial readiness. At the level of international coding systems, ADSS1 myopathy is misclassified under legacy terminology in SNOMED CT and Orphanet and is not independently represented in ICD-11. This position statement argues for harmonization of both gene and variant nomenclature and disease classification. We promote adoption of ADSS1 (HGNC:20093) as the canonical gene symbol, adenylosuccinate synthase 1 (ADSS1) as the canonical protein name, with ADSSL1 retained as a historical synonym, and PURA1 recognized as a protein alias. We further propose classification of ADSS1 myopathy as a metabolic myopathy caused by an inborn error of purine metabolism (more concisely, a metabolic myopathy), with distal and nemaline descriptors retained as histopathological modifiers. Standardization is a low-cost, high-impact intervention that will improve diagnostic accuracy, enable integration of multi-omics datasets, strengthen registries and accelerate therapeutic development for this globally dispersed ultra-rare disease.
Clinical trial number: Not applicable.
Related
- Proposal for a Global Classification and Nomenclature System for A/H9 Influenza Viruses
- Nomenclature, classification, and in-silico structural analysis of MSP1a variants of Anaplasma marginale
- Clinical variables and quantitative CT radiomics for mortality risk stratification after acute exacerbation of idiopathic inflammatory myopathy-associated interstitial lung disease
- The role of 18F-FDG PET-CT in predicting progressive pulmonary fibrosis in idiopathic inflammatory myopathy associated interstitial lung disease
- Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature
BibTeX
@article{rybalka2026harmonizing,
title = {{Harmonizing gene nomenclature and disease classification for ADSS1 myopathy}},
author = {Emma Rybalka and Oleg A. Shchelochkov and Merve Koç Yekedüz and Jaymin Upadhyay and Alan H. Beggs},
journal = {Orphanet Journal of Rare Diseases},
year = {2026},
month = aug,
doi = {10.1186/s13023-026-04535-8},
url = {https://doi.org/10.1186/s13023-026-04535-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Harmonizing gene nomenclature and disease classification for ADSS1 myopathy
AU - Emma Rybalka
AU - Oleg A. Shchelochkov
AU - Merve Koç Yekedüz
AU - Jaymin Upadhyay
AU - Alan H. Beggs
PY - 2026
DA - 2026/08/05
JO - Orphanet Journal of Rare Diseases
DO - 10.1186/s13023-026-04535-8
UR - https://doi.org/10.1186/s13023-026-04535-8
AB - ADSS1 myopathy is an ultra-rare autosomal recessive neuromuscular disorder caused by biallelic pathogenic variants in ADSS1 encoding the striated muscle isozyme of adenylosuccinate synthase involved in purine metabolism. Despite advances in clinical, genetic and mechanistic understanding, the condition remains inconsistently represented across clinical, genomic and registry systems. It is variably labelled as ADSSL1-related distal myopathy, nemaline myopathy, or more recently, a metabolic myopathy reflecting an inborn error of metabolism. These inconsistencies have practical consequences. Gene nomenclature and annotation drift introduces avoidable errors in variant interpretation, panel design and data integration, while imprecise disease classification based on early observations reduces clinical ascertainment of new cases, degrades longitudinal natural history studies, and delays clinical trial readiness. At the level of international coding systems, ADSS1 myopathy is misclassified under legacy terminology in SNOMED CT and Orphanet and is not independently represented in ICD-11. This position statement argues for harmonization of both gene and variant nomenclature and disease classification. We promote adoption of ADSS1 (HGNC:20093) as the canonical gene symbol, adenylosuccinate synthase 1 (ADSS1) as the canonical protein name, with ADSSL1 retained as a historical synonym, and PURA1 recognized as a protein alias. We further propose classification of ADSS1 myopathy as a metabolic myopathy caused by an inborn error of purine metabolism (more concisely, a metabolic myopathy), with distal and nemaline descriptors retained as histopathological modifiers. Standardization is a low-cost, high-impact intervention that will improve diagnostic accuracy, enable integration of multi-omics datasets, strengthen registries and accelerate therapeutic development for this globally dispersed ultra-rare disease. Clinical trial number: Not applicable.
SN - 1750-1172
ER -