Table 1.
Clinical and molecular analyses of two Vietnamese female patients with OTCD.
| Patient 1 | Patient 2 | |
|---|---|---|
| CLINICAL SYMPTOMS | ||
| Age of diagnosis | 12 months | 24 months |
| Initial symptoms | Fever, cough, anorexia, and lethargy. | Vomiting, anorexia, and lethargy. |
| Presenting symptoms | Mechanical ventilation, shock condition, deep coma, both of dilated pupils at 4 mm with weak light reaction. | Coma, no paralysis, no convulsion |
| Family history | Brother died at 4 days of age due to a coma and dyspnea. Parents were asymptomatic. | Uncle, two brothers, and cousin died after birth due to coma and dyspnea. Grandmother died at the age of 35 by a stroke. Aunt died at the age of 21 after delivery due to a coma. Parents and elder sister were asymptomatic. |
| Initial ammonia levels (μg/dL) (Normal: <50) |
1,100 | 259 |
| AST levels (UI L−1) (Normal: 10–40) |
148 | 53 |
| ALT levels (UI L−1) (Normal: 7–59) |
119 | 69 |
| INR | 3.45 | 3.03 |
| Glutamine levels (μmol L−1) (Normal: 530 ± 81) |
1,490 | 579 |
| Lactatemia levels (mmol L−1) (Normal: 1.1–2.3) |
8.3 | 4.75 |
| Urinary orotic levels | Elevated | Elevated |
| Uracil acid levels | Elevated | Elevated |
| Lysine levels (μmol L−1) (Normal: 48–284) |
430 | 135 |
| Phenylalanine levels (μmol L−1) (Normal: 26–91) |
116.8 | 31.7 |
| Brain MRI/CT scanner Findings | Cerebral edema and abnormal T1W | Cerebral edema |
| Management | Stop feeding, glucose infusion (10 mg kg−1 min−1), l-carnitine (100 mg kg−1 day−1), and l-arginine (500 mg kg−1 day−1), and hemofiltration |
Stop feeding, glucose infusion (10 mg kg−1 min−1), l-carnitine (100 mg kg−1 day−1), l-arginine (500 mg kg−1 day−1), and sodium benzoate (500 mg kg−1 day−1) |
| LONG-TERM OUTCOME | ||
| Age | 3 | 4 |
| Development | Delay (DQ = 50%) | Delay (DQ = 50%) |
| Recurrent episodes of hyperammonemia | 5 | 10 |
| MOLECULAR ANALYSES | ||
| Nucleotide change | c.365A>T | c.717+1G>A |
| Position in the OTC gene | Exon 4 | Intron 7 |
| Zygosity | Heterozygous | Heterozygous |
| Maternal status | Carrier | Carrier |
| Effect | Missense | Donor splice site error |
| Amino acid change | p.Glu122Val | – |
| SIFT (score/prediction) | 0 (Deleterious) | – |
| PolyPhen-2 (score/prediction) | 1 (Damaging) | – |
| PANTHER (score/prediction) | 4200 (Probably damaging) | – |
| FATHMM (score/prediction) | −6.61 (Damaging) | – |
| SNPs&GO (score/prediction) | RI 9 (Disease) | – |
| Pmut (score/prediction) | 0.93(94%) (Disease) | – |
| Align-GVGD (score/prediction) | C65 (Pathogenic) | – |
| SNAP2 (score/prediction) | 88 (Effect) | – |
| Mutation assessor (score/prediction) | 4.24 (High impact) | – |
| PROVEAN (score/prediction) | −6.625 (Deleterious) | – |
| CADD (score/prediction) | 34 (Deleterious) | 33 (Deleterious) |
| Mutation Taster (score/prediction) | 0.9999 (Disease causing) | 1 (Disease causing) |
| MaxEntScan | – | 0.94 (Mutant) vs. 9.12 (Wild type) (−89.69% variation) |
| Splice finder | – | 60.43 (Mutant) vs. 87.26 (Wild type) (−30.75% variation) |
| Frequency (1,000 genomes, gnomAD) |
0 | 0 |
| ClinVar | – | Pathogenic (RCV000083542.1) |
| ACMG classification | Likely pathogenic | Pathogenic |
| Human gene mutation database | Novel | HGMD ID CS003075 |