Table 1.
Variables, definitions and values
| Variable | Values (abbreviation) |
|---|---|
| Metabolic defect | • ARG1-D, Arginase 1 deficiency • ASL-D, Argininosuccinate lyase deficiency • ASS-D, Argininosuccinate synthetase deficiency • fOTC-D, female ornithine transcarbamylase deficiency • mOTC-D, male ornithine transcarbamylase deficiency • CITR-D, Citrin deficiency • CPS1-D, Carbamylphosphate synthetase 1 deficiency ASx, asymptomatic • HHH syndr., Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome • NAGS-D, N-Acetylglutamate synthase deficiency |
| Sex | male/female |
| Mode of diagnosis | • Prenatal testing (PT) • Newborn screening (NBS) • High-risk family screening (FH) • Metabolic investigation after onset of symptoms (SX) |
| Ages and times | • Age at diagnosis, if detected by PT set as zero (no prenatal UCD treatment) • Age at first symptoms • Age at last visit • Diagnostic delay (age at diagnosis minus age at first symptoms; negative when diagnosed pre-symptomatically, positive when symptomatic before diagnosis) • Observation period (time last visit minus time study inclusion) |
| Survival | Yes/no |
| Changing from asymptomatic to symptomatic state | Yes/no |
| Mode of confirmation of diagnosis | • Enzyme analysis • Metabolite analysis including amino acids • Mutation analysis • Pedigree analysis |
| Onset | • Early onset (EO; ≤ 28 days) • Late onset (LO; > 28 days) • Asymptomatic (AS) |
| Symptomatic state | Yes/no E-IMD definition: showing clinical symptoms associated with the respective diagnosis UCDC definition: symptoms associated with plasma ammonium concentrations > 100 μmol/L and/or liver transplant and/or ≥ 2 signs and symptoms: recurrent vomiting, protein intolerance, episodic lethargy, developmental and/or intellectual disabilities, abnormal neurological examination, brain edema on cranial MRI or CT scan, chronic migraine, and/or (episodic) psychosis |
| Signs and symptoms leading to the diagnosis unique to the E-IMD registry | • Blood abnormalities • Hyperexcitability • Impaired consciousness • Muscular hypertonia • Muscular hypotonia • Neurology other than seizures • Seizures • Sepsis-like appearance • Vomiting and feeding problems |
The following variables were used in UCDC and E-IMD for combined and comparative analysis between NA and EU.