PNPO Deficiency and Cirrhosis: Expanding the Clinical Phenotype?

D Coman; P Lewindon; P Clayton; K Riney

doi:10.1007/8904_2015_456

PNPO Deficiency and Cirrhosis: Expanding the Clinical Phenotype?

JIMD Rep. 2016:25:71-75. doi: 10.1007/8904_2015_456. Epub 2015 Jun 25.

Authors

D Coman^{1

2

3}, P Lewindon^{4

5}, P Clayton⁶, K Riney^{7

4}

Affiliations

¹ Neuroscience Department, The Lady Cilento Children's Hospital, Brisbane, QLD, Australia. [email protected].
² School of Medicine, The University of Queensland, Brisbane, QLD, Australia. [email protected].
³ School of Medicine, Griffith University, Gold Coast, QLD, Australia. [email protected].
⁴ School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁵ Gastroenterology Department, The Lady Cilento Children's Hospital, Brisbane, QLD, Australia.
⁶ UCL Institute of Child Health, London, UK.
⁷ Neuroscience Department, The Lady Cilento Children's Hospital, Brisbane, QLD, Australia.

Abstract

We report the case of a 4-year-old boy with pyridoxamine 5-phosphate oxidase deficiency, now the second reported case to develop hepatic cirrhosis. He presented with an encephalopathy in the first 1.5 h of life and received a first dose of PLP at 40 h of life. PNPO gene sequencing identified homozygosity for a novel variant in exon 7, c.637C>T (p.Pro213Ser). Persistent elevations in alanine transferase and aspartate transferase combined with an echogenic liver on ultrasound prompted performance of a liver biopsy which demonstrated hepatic cirrhosis. This is the second reported case of hepatic cirrhosis in PNPO deficiency. The pathogenesis is unclear but may be related to epigenetic activation of purinergic signaling in the hepatic stellate cells. PNPO deficiency may in time prove to be a suitable candidate for consideration of therapeutic orthotropic liver transplantation in select patients.