# Liver transplantation can prevent the progression of neurological damage in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome and maintain long-term metabolic stability — The largest single-center experience

## TL;DR

Liver transplantation can stop neurological damage and stabilize metabolism in a rare genetic disorder called HHH syndrome, especially when done early.

## Contribution

The study presents the largest single-center experience showing liver transplantation's effectiveness in treating HHH syndrome.

## Key findings

- Liver transplantation normalized metabolic parameters and allowed patients to resume normal diets.
- Early transplantation improved neurological function in 83.3% of patients, including reduced spasticity and improved walking.
- Quality-of-life scores improved in 33.3% of patients, with an 83.3% overall survival rate.

## Abstract

Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome is a rare urea cycle disorder caused by mutations in the SLC25A15 gene, leading to metabolic and neurological impairments. Liver transplantation (LT) may restore urea cycle function and prevent disease progression.

This retrospective study analyzed six patients with HHH syndrome who underwent LT between 2016 and 2022. Pre- and post-transplant evaluations included biochemical tests, genetic analysis, neurological assessments, and quality-of-life measures.

LT successfully normalized metabolic parameters (ammonia and amino acid levels) and allowed patients to resume normal diets. Early transplantation resulted in neurological improvement in 5 of 6 patients (83.3%), including reduced lower limb spasticity and improved walking ability. Two patients (33.3%) achieved nearly normal gait, and one patient (16.7%) recovered to normal motor function within three months after LT. Quality-of-life scores improved in 2 patients (33.3%). The overall survival rate was 83.3%, with one patient dying from unrelated causes 5 years post-transplant. No significant long-term complications were observed in the surviving patients.

Liver transplantation is an effective treatment for HHH syndrome, halting neurological decline and improving quality of life. Early LT before irreversible damage provides the best outcomes, making it a viable option for patients with progressive symptoms unresponsive to conventional therapies.

Not applicable.

The online version contains supplementary material available at 10.1186/s13023-025-04077-5.