Webster, Richard;
Sankaran, Bindu Parayil;
Bandodkar, Sushil;
Stormon, Michael;
Thomas, Gordon;
Shun, Albert;
Bowen, David Geoffrey;
... Bhattacharya, Kaustuv; + view all
(2026)
Liver Transplantation in PNPO Deficiency: Management Challenges and Biological Lessons.
JIMD Reports
, 67
(1)
, Article e70067. 10.1002/jmd2.70067.
Preview |
PDF
JIMD Reports - 2026 - Webster - Liver Transplantation in PNPO Deficiency Management Challenges and Biological Lessons.pdf - Published Version Download (577kB) | Preview |
Abstract
Pyridox(am)ine 5′ Phosphate Oxidase deficiency (PNPO) presents with refractory epilepsy responsive to treatment with pyridoxal 5′ phosphate (PLP) or pyridoxine. A 15-year-old boy with PNPO deficiency and cirrhosis underwent orthotopic liver transplantation for hepatocellular carcinoma without extra-hepatic disease. Pre-transplant, the boy was cognitively normal with well controlled epilepsy on PLP 50 mg/kg/day. Continuous EEG monitoring was used pre-operatively and post-operatively to identify encephalopathy resulting from PLP deficiency. B6 vitamers (pyridoxine [PN], pyridoxamine [PM], pyridoxal [PL] and phosphorylated forms [PNP, PMP, PLP]) were assayed at times of encephalopathy (symptoms and/or EEG) and for pharmacokinetics. Doses of PLP were titrated to prevent encephalopathy and limit side effects. The intraoperative/immediate postoperative periods were managed with intravenous PLP at a dose which could be reduced to 7.8 mg/kg/day before encephalopathy recurred. Post-transplant, transition to oral PLP (100 mg/kg/day) led to fulminant hepatic impairment, which improved when IV dosing resumed. Subsequent transition to full oral PLP dosing took 9 months with a final dose of 24 mg/kg/day oral PLP. PLP showed dose dependent hepatotoxicity with associated rises in alpha-fetoprotein levels. Gradual PLP dose changes and frequent oral dosing minimised encephalopathy episodes and hepato-toxicity. Six years post-transplant, liver biopsy showed moderate portal fibrosis (Ishak fibrosis stage 2/6, LAFSc score 3/9). Encephalopathy/seizures were associated with lower plasma PL concentrations (40 times above physiological levels); but high plasma PLP concentrations did not prevent encephalopathy. Despite liver transplantation, requirements for supraphysiologic doses of PLP continued, suggesting impaired neuronal PLP salvage is the major factor determining PLP requirements in PNPO deficiency.
| Type: | Article |
|---|---|
| Title: | Liver Transplantation in PNPO Deficiency: Management Challenges and Biological Lessons |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jmd2.70067 |
| Publisher version: | https://doi.org/10.1002/jmd2.70067 |
| Language: | English |
| Additional information: | © 2026 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | cirrhosis, hepatocellular carcinoma, liver transplantation, PLP associated hepatotoxicity, PNPO deficiency, vitamin B6 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10220007 |
Archive Staff Only
 |
View Item |
