Long and short term biochemical and clinical follow-up after liver transplantation in three patients with mild Zellweger disorder

Zellweger spectrum disorders (ZSD) are attributable to mutations in PEX genes. The clinical course is characterised by progressive hearing and vision loss, and neurodevelopmental delay. Currently supportive treatment is the standard since neither plasmalogen supplementation, low phytanic acid diet, cholic acid nor docosahexaenoic acid have shown clinical benefits. Liver transplantation (LT) has been performed by us in three mild ZSD patients, two of them showed neurodevelopmental improvement while the third died due to unrelated causes soon after the LT. We present our long term (17 years post-LT, patient 1) and short term (7 months post-LT, patient 3) follow-up experience of the two survivors, wherein we document a sustained improvement in biochemical profile, with a complete normalisation of phytanic acid level. The metabolic control was associated with improved clinical evolution, puberty achievement, stabilisation of neurodevelopmental status which have allowed for a relatively autonomous lifestyle in the long term. The allograft outcome in children with mild ZSD was not different or inferior to LT performed for other indications. We propose that LT before onset of severe sensorineural defects in mild ZSD offers a new therapeutic option which results in metabolic remission and subsequent improved long term clinical outcomes.