IEMbase 0014: ASS1-related argininosuccinate synthetase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 14 |
| Nosology | 1.1.04.01 |
| Gene | ASS1 |
| External IDs | OMIM:215700 |
| Generated mapping | AMBIGUOUS by alias_exact:argininosuccinate synthetase deficiency |
| Candidate DisMech targets | Citrullinemia_Type_I.yaml; Urea_Cycle_Disorder.yaml#Argininosuccinate Synthetase Deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as classical citrullinemia/CTLN1. The characteristic clinical signal is acute hyperammonemic encephalopathy with coma and developmental delay, plus stroke-like episodes. Additional features include neonatal seizures, vomiting, feeding difficulty/protein aversion, failure to thrive, episodic confusion, ataxia, burst-suppression EEG, acute liver failure, and neonatal temperature instability.
The biochemical profile distinguishes ASS1 deficiency from other UCDs: very high plasma and urine citrulline, high ammonia, high plasma/CSF glutamine, low arginine, normal urinary argininosuccinic acid, variably high orotic acid, and low/normal urea. Treatments include arginine, protein-defined diet, nitrogen scavengers, hemodialysis, peritoneal dialysis, and liver transplantation.
DisMech phenotype coverage
Citrullinemia_Type_I.yaml is the correct canonical target. It covers
hyperammonemia, encephalopathy, seizures, lethargy, poor feeding, vomiting,
intellectual disability, global developmental delay, cerebral edema, spasticity,
coma, failure to thrive, and respiratory alkalosis. Biochemical coverage is
strong: citrulline, ammonia, arginine, argininosuccinate, orotic acid, and
glutamine are all explicit. Treatments include diet, nitrogen scavengers,
arginine, acute crisis management, liver transplantation, newborn screening,
genetic counseling, and emerging RNA therapeutics.
The Urea Cycle Disorder subtype duplicates the exact disease label and causes
the generated ambiguity.
Concordance and completeness
Judgement: high concordance. DisMech has the right standalone entry and covers the major clinical and biochemical axes.
IEMbase adds more age-stratified presentation detail, burst-suppression EEG, stroke-like episodes, temperature instability, and explicit dialysis modalities. DisMech adds cerebral edema, respiratory alkalosis, newborn screening, and an investigational RNA-therapeutic angle not present in IEMbase.
Curation actions
- Resolve crosswalk ambiguity by mapping to
Citrullinemia_Type_I.yaml. - Consider whether burst-suppression EEG and protein aversion should be added as evidence-backed phenotype refinements.
- Keep the umbrella subtype as secondary context only.