The effect of liver transplantation for argininemia-the largest experiences in a single center

Abstract

Background: Argininemia, a rare urea cycle disorder resulting from an arginase-1 deficiency, is characterized by a progressive spastic paraplegia. While advances in diagnosis and treatment have increased the management of this condition, not all symptoms are resolved in response to traditional therapies. Interestingly, there exist some rare reports on the use of liver transplantation (LT) for the treatment of argininemia.

Methods: We conducted a retrospective study of eleven patients with argininemia receiving a LT as performed at our center over the period from January 2015 to November 2019. These patients were included due to their poor responses to protein restriction diets and alternative therapies of nitrogen scavengers. Detailed information on coagulation, liver function, histopathological and morphological examination of liver samples, and other clinical presentations were extracted from these patients. A grading scale was used for evaluating the neurological status, classification of physical growth and quality of life of these patients in response to the LT.

Results: Prior to LT, high levels of arginine were detected in all of argininemia patients and liver enzymes were elevated in nine of those patients. Nine patients presented with coagulation dysfunction without bleeding symptoms. Spastic paraplegia, irritability, intellectual developmental disability, and growth deficits were hallmarks of these nine patients, while four patients showed repeated, generalized tonic-clonic seizures before the operation. Seven novel mutations were found in these patients. The indication for LT in this series of patients was a presentation of progressive neurological impairments. After LT, the coagulation index and plasma arginine levels returned to normal and episodes of seizure were controlled in four patients. To date, all patients have survived and their LT has resulted a restoration of arginine metabolism and liver function, along with preventing further neurological deterioration, all of which provided an opportunity for future recuperation. Overall, the neurological status, growth deficits and quality of life were all significantly improved after LT with no evidence of severe complications.

Conclusions: LT can serve as an effective treatment for argininemia in patients who respond poorly to traditional therapy. An early intervention of LT should be conducted in these patients to prevent neurological damage and improve their quality of life.

Keywords: Argininemia; liver transplantation (LT); neurological damage; urea cycle disorders (UCDs).

Figure 1

Pathological characteristics within the liver of argininemia patients. (A) Hematoxylin-eosin (HE) staining showing swollen “ballooned” hepatocytes, patchy fatty vacuolars, lymphocytes infiltration within portal areas. (B) Electron microscopy showing damaged hepatocytes with substantial swelling, an increased number of mitochondria with unclear ultrastructures and diffuse lipid droplets, while the shape and disposition of the endoplasmic reticulum appeared normal.

Video S1

The walking posture improved significantly in case 7 after the operation.