Table 3.
Part 1 OTCD Cases at Children's Hospital Colorado
| Case No. Current status/Rx Liver Injury |
Gender | Age | Presentation | AST IU/L |
ALT IU/L |
PT sec |
INR | PTT sec |
Bili | NH3 umol/L |
V | VII | VIII | Liver histology | Fibrinogen | D- dimers |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neonatal Males | ||||||||||||||||
| 1 Deceased ALF |
M | 4 d | 3 day h/o increased RR, progressive encephalopathy | 104 | 81 | 37.6 | 3.83 | 65 | 6.0 | 2634 | ND | ND | ND | ND | 71 | 5.73 |
| 2 Deceased ALF |
M | 2 d | Increased RR, jitteriness, progressive encephalopathy | 91 | 22 | 35.6 | 3.3 | >250 Dialysis | 10.0 | 2125 | ND | ND | ND | ND | 119 | 1.62 |
| 3 Deceased ALF |
M | 2 d | Respiratory distress, lethargy | ND | ND | 24.3 | ND | 39.3 | 5.1 | 1398 | ND | ND | ND | Normal | 140 | ND |
| 4 Deceased ALF |
M | 2 d | Increased RR, twitching, apnea | 45 | 32 | 24.0 | 2.1 | 45 | 8.4 | 1308 | ND | ND | ND | OTC enzyme activity 2%. Microvesicular steatosis, mild cholestasis | 112 | 3.64 |
| 5 Deceased LD |
M | 2 d | Poor feeding, lethargy | 37 | 130 | 17.0 | 1.57 | 109 | 3.1 | 24 (peak 1939) | ND | ND | ND | ND | 108 | 1017 |
| 6 Tx LD HCI |
M | 2 d | Emesis | 467 | 256 | 17.8 | 1.43 | 39 | 5.4 | 1152 | ND | ND | ND | Unremarkable | 214 | 1.79 |
| Severe OTCD | ||||||||||||||||
| 7 Tx ALF HCI |
F | 1 year | Liver failure, h/o emesis, “reflux” (Had multiple later HA events without LF) |
4139 | 2089 | 63.7 | 5.7 | 49.9 | 0.4 | 207 | ND | ND | ND | Microvesicular steatosis, mild inflammation, mild portal fibrosis | ND | ND |
| 8 Tx ALF HCI |
F | Prenatal | Known family history, liver failure at 2 years | 2232 | 2127 | 23.8 | 2.52 | 45 | 0.8 | 49 (was > 100) | 55 (low) | 9.2 (low) | 230 | OTC enzyme activity 4% Increased glycogen, no fibrosis, diffuse microvesicular steatosis | 263 | 333 |
|
ALF
HCI |
Same pt as above | Same pt as above | Same pt as above | 1538 | 1165 | 21.5 | 1.8 | 45.4 | 1.2/0.5 | 40 (was 178) | ND | ND | ND | Same pt as above | ND | ND |
|
ALF
HCI |
Same pt as above | Same pt as above | Same pt as above | 2401 | 1692 | 23.6 | 1.97 | 43.6 | 0.5 | 216 | 39.9 (low) | 17.7 (low) | 130.2 | Same pt as above | ND | < 200 |
|
ALF
HCI |
Same pt as above | Same pt as above | Same pt as above | 74 (went up to 869) | 178 (went up to 997) | 52.3 | 3.76 | 58.5 | 0.4 | 171 | 60.4 (low) | <4.0 (low) | 192 | Same pt as above | 227 | < 230 |
| 9 Tx ALF HCI |
F | 5 years | Emesis, lethargy with UTIs | 377 | 1083 | 19 | 2.4 | ND | ND | ND | ND | ND | ND | OTC enzyme activity 7.8% Diffuse glycogenation of hepatocytes with minimal portal fibrosis | ND | ND |
|
ALF
HCI |
Same pt as above | Same pt as above | Same pt as above | 57 | 446 | 18.8 | 2.66 | ND | ND | ND | ND | ND | ND | Same pt as above | ND | ND |
|
ALF
HCI |
Same pt as above | Same pt as above | Same pt as above | 1212 | 1749 | 28.4 | ND | ND | 1.1/0.4 | 41 (was 167) | 49 (low) | 19 (low) | ND | Same pt as above | ND | ND |
| LD | Same pt as above | Same pt as above | Same pt as above | ND | ND | 15.7 | 1.52 | ND | ND | 88 (was 118) | ND | ND | ND | Same pt as above | ND | ND |
| 10 Diet/Bu/Cit LD HCI |
F | 3 years | 2 year h/o emesis, AMS, recurrent vision loss | 2039 | 1605 | 17.5 | 1.39 | 40 | 0.8 | 111 (was 410) | ND | ND | ND | ND | 227 | 1.09 |
| 11 Tx No liver injury |
F | 4 years | Mother died of OTCD | 20 | 41 | 14.9 | 1.29 | 37.3 | 0.4 | 106 | ND | ND | ND | Path at tx – mild peripoprtal fibrosis, patchy centrilobular architectural collapse | ND | ND |
| 12 Tx No liver injury |
F | 3 d | Lethargy and poor feeding, progressive encephalopathy | 80 | 169 | ND | ND | ND | 0.4 | 192 | ND | ND | ND | OTC activity very low Ballooning hepatocytes, multinucleation granular cytoplasm, minimal periportal fibrosis | ND | ND |
| Moderate OTCD | ||||||||||||||||
| 13 Diet/Bu/Arg ALF HCI |
M | 3 years | Recurrent emesis | 615 | 1938 | 22.8 | 1.84 | 38 | 0.2/0.0 | 46 (was 160) | ND | ND | ND | OTC activity 10% Patchy ballooning hepatocytes, glycogneated nuclei | ND | ND |
|
ALF
HCI |
Same pt as above | Same pt as above | See above | ND | 1088 | ND | 2.1 | ND | ND | ND | ND | ND | ND | Same pt as above | ND | ND |
| HCI | Same pt as above | Same pt as above | See above | ND | 1530 | ND | ND | ND | ND | ND | ND | ND | ND | Same pt as above | ND | ND |
| 14 Diet/Bu/Arg ALF HCI |
M | 3 years | Illness, affected sib | 785 | 1223 | 34.9 | 3.1 | 48 | 0.3 | 108 | ND | ND | ND | ND | ND | ND |
| Mild OTCD | ||||||||||||||||
| 15 Diet/Be/Cit LD |
F | 2 years | Altered mental status | 41 | 67 | 17.6 | 1.4 | 55 | 0.4 | 198 | ND | ND | ND | ND | ND | ND |
| 16 LD Arg |
M | 11 y | Valproate induced hyperammonema h/o autism, delay, recurrent emesis | 14 | 14 | 15.6 | 1.21 | 29 | 0.1 | 144 | ND | ND | ND | ND | ND | ND |
| LD | Same pt as above | Same pt as above | Same pt as above | 23 | 10 | 16 | 1.28 | 33 | 0.4 | <9 | ND | ND | ND | Same pt as above | 232 | ND |
| 17 Cit LD |
F | NA | Family history, brother with neonatal OTC | 18 | 27 | 15.4 | 1.16 | 30 | 0.6 | 91 | ND | ND | ND | ND | ND | ND |
| LD | Same pt as above | Same pt as above | Same pt as above | 17 | 27 | 15.8 | 1.28 | 32 | 0.7 | 99 | ND | ND | ND | Same pt as above | 236 | ND |
| LD | Same pt as above | Same pt as above | Same pt as above | 21 | 28 | 15.3 | 1.18 | 31 | 0.9 | 35 | ND | ND | ND | Same pt as above | ND | ND |
| LD | Same pt as above | Same pt as above | Same pt as above | 26 | 43 | 15.6 | 1.22 | 30 | 1.2 | ND | ND | ND | ND | Same pt as above | 281 | ND |
| 18 Bu/Cit LD |
F | 2 y | Intermittent ataxia, abnormal eye movements, family history, brother with neonatal OTC | 43 | 31 | 15.1 | 1.16 | 39 | 0.3 | 48 | ND | ND | ND | ND | ND | ND |
| LD | Same pt as above | Same pt as above | Same pt as above | 25 | 18 | 15.2 | 1.14 | 33 | 0.5 | 56 | ND | ND | ND | Same pt as above | ND | ND |
| LD | Same pt as above | Same pt as above | Same pt as above | 26 | 14 | 15.4 | 1.19 | 37 | 0.4 | 36 | ND | ND | ND | Same pt as above | 175 | ND |
| 19 Arg HCI |
M | 1st year | Recurrent emesis, increased AST/ALT | 519 | 689 | ND | ND | ND | 0.2/0.8 | ND | ND | ND | ND | Scattered individual hepatocytes with nonspecific degeneration | ND | ND |
| 20 No Rx HCI |
M | Neonatal presentation, suspected mosaic due to current status | 150 | 317 | 13.6 | 1.26 | 35 | 0.5 | 33 | ND | ND | ND | ND | ND | ND | |
| 21 Bu/Arg No liver injury |
F | 27 y | Son with neonatal OTCD | 30 | 14 | 14.0 | 1.04 | 28 | 0.6 | 23 | ND | ND | ND | ND | 208 | ND |
| 22 No current Rx, was on Bu/Arg No liver injury |
F | 37 y | Family history, possible seizures | 23 | 39 | 13 | 0.95 | 29 | 0.2 | 29 | ND | ND | ND | ND | 271 | ND |
| No Symptoms/Treatment | ||||||||||||||||
| 23 No Rx LD |
F | NA | Family history | 12 | 14 | 16.2 | 1.27 | 32 | 0.4 | 57 | ND | ND | ND | ND | 195 | ND |
| 24 No Rx LD |
F | NA | Family history | 51 | 44 | 15.6 | 1.21 | 33 | 0.4 | 40 | ND | ND | ND | ND | 201 | ND |
| 25 No Rx No liver injury |
M | 10 y | Brother with hyperammonemia | 37 | 19 | 14.2 | 1.09 | 32 | 0.7 | 22 | ND | ND | ND | ND | 252 | ND |
| 26 No Rx No liver injury |
F | NA | Family history | 34 | 49 | 13.3 | 0.98 | 30 | 0.3 | <9 | ND | ND | ND | ND | 304 | ND |
| 27 No Rx No liver injury |
F | NA | Family history | 19 | 11 | 12.7 | 0.92 | 29 | 0.3 | 13 | ND | ND | ND | ND | 369 | ND |
| 28 Cit since birth, Asx No liver injury |
F | NA | Affected brother | 62 | 21 | 13.4 | 0.98 | 30 | 1.2 | 20 | ND | ND | ND | ND | 249 | ND |
| 29 No Rx No liver injury |
F | NA | Three affected children | 20 | 12 | 13.1 | 0.96 | 32 | 0.5 | 57 | ND | ND | ND | ND | 351 | ND |
| 30 No Rx No liver injury |
F | 37 | Affected son | 34 | 19 | 13.6 | 1.01 | 29 | 0.5 | 39 | ND | ND | ND | ND | 285 | ND |
| 31 No Rx No liver injury |
F | 21 | Affected son | 15 | 12 | 12.8 | 0.94 | 29 | 0.4 | < 9 | ND | ND | ND | ND | 342 | ND |
| Table 3 Part 2. OTCD Cases at UCLA. | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case No. Current status/Rx Liver Injury |
Gender | Age | Presentation | AST IU/L |
ALT IU/L |
PT sec |
INR | PTT sec |
Bili | NH3 umol/L |
V | VII | VIII | Liver histology |
Fibrinogen | D- dimers |
| Neonatal Males | ||||||||||||||||
| 1 Deceased ALF |
M | 2 d | Poor feeding, lethargy, then seizure, then apnea, and then NH3 = 1734. | 202 | 188 | 32.9 | 3.2 | 151.2 | 14.1/1.9 | 1293 | ND | ND | ND | ND | 67 | ND |
| 2 Deceased ALF |
M | 9 d | Pulmonary hemorrhage on DOL 3, hyperammonemia on DOL 9. | 138 | 94 | 22.8 | 2.3 | 38.7 | 25.2/14.6 | 1744 | 19.9% act. | 19.6% act. | ND | Hepatomegaly, splenomegaly; green, homogeneous liver parenchyma, geographic fibrosis with bile stasis noted. | 158 | ND |
| 3 Tx ALF HCI |
M | 1 d | Brother had passed away of OTC, lethargy on DOL 1, needed hemodialysis. | 406 | 242 | 32.6 | 6.4 | >180 | 8.2/5.8 | 256 | ND | ND | ND | Diffuse macro and micro vesicular steatosis, moderate cholestasis, no evidence of hepatitis. | 66 | ND |
| 4 Tx No Liver Injury |
M | 2 d | Poor feeding, irritable, hyperammonemia, coma by 36 hours of life | 93 | 93 | 14.3 | 1.1 | 41 | 4.3 | 143 | ND | ND | ND | ND | ND | ND |
| 5 Diet/Bu/Be No Liver Injury |
M | prenatal | Diagnosed in utero (mother is OTC carrier), neonatal seizures. | 49 | 39 | 10.8 | 1.1 | 31.3 | 0.6 | 41 | ND | ND | ND | ND | 159 | ND |
| 6 Tx No Liver Injury |
M | 1 d | Poor feeding and lethargy at 24–30 hours of life. | 25 | 22 | 8.6 | 0.9 | 26 | 2.2/1.0 | 754 | ND | ND | ND | 233 | ND | |
| Severe OTCD | ||||||||||||||||
| 7 Diet/cit/arg/Be/Ac ALF HCI |
F | 5 y | Increased irritability with ketosis. | 419 | 900 | 37.7 | 3.5 | 62 | 0.6 | 133 | ND | ND | ND | ND | ND | ND |
|
ALF
HCI |
Same pt as above | Same pt as above | See above | 3204 | 4407 | 26.3 | 2.4 | 43 | 1.4 | 492 | ND | ND | ND | ND | 176 | 2 |
| 8 Diet/Bu/Cit ALF HCI |
F | 1 yo 7 m | Presented with h/o chronic n/v, with acute fever, vomiting, seizures found to be in acute liver failure. | 1932 | 2042 | 39.5 | 4.1 | 39.9 | 0.4/0.1 | 220 | 70% | 11% act. | 211% act | Acute hepatocellular injury with mild lobular necrosis, paucity of inflammatory infiltrate. | 245 | ND |
|
ALF
HCI |
Same pt as above | Same pt as above | Same pt as above | 6299 | 5519 | 21.4 | 2.1 | 35.1 | 0.3 | 443 | 39% | 13% | ND | ND | 228 | ND |
| 9 Diet/Bu/Arg Carnitine No Liver Injury |
F | 6 y | Reccurent abd pain/n/v/ataxia. | 16 | 16 | 10.6 | 1 | 27.8 | 0.4 | 174 | ND | ND | ND | ND | 242 | ND |
| Moderate OTCD | ||||||||||||||||
| 10 Diet/Bu/Cit HCI |
F | 3 yo 7 m | AGE with persistently elevated AST/ALT | 59 | 216 | 11.9 | 1.2 | 31.3 | 0.5 | 253 | ND | ND | ND | ND | 236 | ND |
| HCI | Same pt as above | Same pt as above | Same pt as above | 309 | 65 | ND | ND | ND | 0.6 | ND | ND | ND | ND | ND | ND | ND |
| 11 Diet/Be LD) |
F | 12 m | Lethargy, hyperammonemia, left sided weakness, multiple, bilateral foci of stroke R>L. | 123 | 167 | 17.5 | 1.8 | 30.2 | 0.5 | 97 | ND | ND | ND | ND | 181 | ND |
| 12 Diet/Bu LD |
M | 20 m | Chronic emesis, elevated ammonia. | 21 | 25 | 15.2 | 1.5 | 26 | 0.5 | 235 | ND | ND | ND | ND | 206 | ND |
| 13 Diet/Be/Cit LD HCI |
F | 13 m | Fever, emesis × 5 mo, lethargy, irritability, elevated liver enzymes, coagulopathy. | 337 | 959 | 16.6 | 1.7 | 53 | 0.2 | 159 | ND | ND | ND | ND | 305 | ND |
| 14 Diet/Bu No Liver Injury |
F | 4 y | N/v + FH of OTC. in brother | 11 | 13 | 11.6 | 1.1 | 26.3 | 0.4 | 213 | ND | ND | ND | ND | 192 | ND |
| 15 Diet/Bu No Liver Injury |
M | 9 y | Occasional lethargy and inability to function, hyperammonemia. | 14 | 25 | 10.6 | 1 | 27.2 | 0.6 | 132 | ND | ND | ND | ND | 222 | ND |
| 16 Diet No Liver Injury |
M | 13 m | URI + lethargy, hyperammonemia. | 102 | 191 | 11.4 | 1.1 | 28 | 0.5 | 214 (later 332) | ND | ND | ND | ND | 198 | ND |
| 17 Diet/Cit No Liver Injury |
M | 12 y | Hyperammonemia with coma. | 18 | 28 | 11.4 | 1.1 | 30 | 0.8 | 55 | ND | ND | ND | ND | 165 | ND |
| 18 Diet/BuCit No Liver Injury |
F | ND | ND | 20 | 13 | 10.4 | 1 | 26 | 0.4 | 38 | ND | ND | ND | ND | 226 | ND |
| 19 Diet/Cit/Arg Carnitine No Liver Injury |
F | 16–20 m | Hyperammonemia and coma. | 14 | 21 | 10.8 | 1.1 | 29.6 | ND | 86 | ND | ND | ND | ND | 285 | ND |
| Mild OTCD | ||||||||||||||||
| 20 Diet/Bu HCI |
F | 7 yo 2 m | Frank confusion and hyperammonemia with h/o intermittent abdominal pain and nausea. | 97 | 252 | 11.3 | 1.1 | ND | 0.3 | 27 (was 297) | ND | ND | ND | ND | ND | ND |
| 21 Diet/Be/Cit No Liver Injury |
F | 1 y | Nausea/vomiting + FH with sister with OTC. | 41 | 14 | ND | ND | ND | 0.4 | 35 | ND | ND | ND | ND | 226 | ND |
| 22 Diet/BuArg No Liver Injury |
F | 2 m | FH of brother with OTC | 25 | 20 | 11.3 | 1.2 | ND | ND | 55 | ND | ND | ND | ND | ND | ND |
| 23 Diet/Be/Cit/Carnitine No Liver Injury |
M | 3 y 2 m | Lethargy, hyperammonemia, nausea, vomiting, and history of headache head hitting and decreased attention. | 24 | 11 | 10.7 | 1 | 29.6 | 0.7 | 42 | ND | ND | ND | ND | 253 | ND |
| 24 Deceased No Liver Injury |
M | 13 y 11 m | H/o learning disabilities, and schizoaffective disorder, lethargy, coma, hyperammonemia, brain herniation | 78 | 63 | 13.4 | 1.4 | 43 | 0.4/0.1 | 2372 | ND | ND | ND | Hepatomegaly (3030g), diffuse micro and macrovesicular steatosis. | ND | ND |
| 25 Diet/Bu No Liver Injury |
F | 9 m | Stroke and hyperammonemia | 14 | 10 | ND | ND | ND | 0.3 | 63 | ND | ND | ND | ND | ND | ND |
| 26 No Rx No Liver Injury |
M | 30 y | Coma with Meclizine + FH (brother with OTC) | 14 | 22 | 10.4 | 1 | 30.5 | ND | 32 | ND | ND | ND | ND | 335 | ND |
| 27 Diet/Cit No Liver Injury |
F | ND | Infrequent irritability, + FH (3 sisters with OTC) | 23 | 18 | 11.8 | 1.1 | 30.5 | 2.1 | 60 | ND | ND | ND | ND | ND | ND |
| No Symptoms/Treatment | ||||||||||||||||
| 28 No Rx No Liver Injury |
F | N/A | Family History | 12 | 11 | 10.8 | 1.1 | 27 | 0.4 | 65 | ND | ND | ND | ND | 282 | ND |
| 29 No Rx No Liver Injury |
F | N/A | Family History | 15 | 15 | 10.4 | 1 | 27.9 | 0.4 | 39 | ND | ND | ND | ND | 245 | ND |
| 30 No Rx No Liver Injury |
F | N/A | Family History | 12 | 13 | 10.4 | 1 | 25.9 | 0.4 | 43 | ND | ND | ND | ND | 319 | ND |
| 31 No Rx No Liver Injury |
F | N/A | ADHD and Family History | 17 | 26 | 10.6 | 1 | 28 | 0.7 | 49 | ND | ND | ND | ND | 249 | ND |
| 32 No Rx No Liver Injury |
F | N/A | Family History | 10 | 11 | 11 | 1.1 | 29.1 | 0.5 | 40 | ND | ND | ND | ND | 230 | ND |
| 33 No Rx No Liver Injury |
F | N/A | Family History | 21 | 18 | 10.1 | 1 | 28.3 | 0.5 | 37 | ND | ND | ND | ND | 298 | ND |
| 34 No Rx No Liver Injury |
F | N/A | Family History | 10 | 11 | 10.7 | 1 | 28.9 | 0.3 | 23 | ND | ND | ND | ND | 341 | ND |
| 35 No Rx No Liver Injury |
F | N/A | Family History (son) | 14 | 17 | 11 | 1.1 | 27.5 | 0.5 | 26 | ND | ND | ND | ND | 310 | ND |
| 36 No Rx No Liver Injury |
F | N/A | Family History (son) | 24 | 22 | 10.5 | 1 | 25.9 | 0.5 | 34 | ND | ND | ND | ND | 217 | ND |
| 37 No Rx No Liver Injury |
F | N/A | Family History | 20 | 16 | 11.2 | 1.1 | 24.5 | 0.6 | 25 | ND | ND | ND | ND | 142 | ND |
| 38 No Rx No Liver Injury |
F | N/A | Family History | 14 | 12 | 10.8 | 1 | 26.7 | 0.5 | 105 | ND | ND | ND | ND | 250 | ND |
| 39 No Rx No Liver Injury |
F | N/A | Family History | 20 | 20 | 10.6 | 1 | 28.7 | 1.1 | 32 | ND | ND | ND | ND | 256 | ND |
| 40 No Rx No Liver Injury |
M | N/A | Family History (daughters) | 24 | 25 | 11.7 | 1.2 | 29.4 | 1 | 78 | ND | ND | ND | ND | 212 | ND |
Legend: LF: Acute liver failure. LD: Liver dysfunction. HCI: Hepatocellular injury. RR: Respiratory rate. Rx: Treatment. Tx: Liver transplant. ND: Not done. AMS: Altered mental status. Diet: Dietary therapy, restriction of natural protein +/− use of essential amino acids. Arg: Arginine therapy. Cit: Citrulline therapy. Bu: Sodium phenylbutyrate. Be: Sodium benzoate. Asx: Asymptomatic. NH3: Ammonia. HA: Hyperammonemic.
Legend: ALF: Acute liver failure. LD: Liver dysfunction. HCI: Hepatocellular injury. RR: Respiratory rate. Rx: Treatment. Tx: Liver transplant. ND: Not done. AMS: Altered mental status. Diet: Dietary therapy, restriction of natural protein +/− use of essential amino acids. Arg: Arginine therapy. Cit: Citrulline therapy. Bu: Sodium phenylbutyrate. Be: Sodium benzoate. Asx: Asymptomatic. NH3: Ammonia. HA: Hyperammonemic. N/v: Nausea and vomiting. DOL: day of life. FH: Family History. URI: Upper respiratory tract infection. ADHD: Attention deficit hyperactivity disorder.