Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation

J Neurol Neurosurg Psychiatry. 2001 Nov;71(5):663-70. doi: 10.1136/jnnp.71.5.663.


Objective: Adult onset type II citrullinemia is an inherited disorder of amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. Most of the patients with this disease were reported in Japan and therefore, this disease has not been well recognised outside this country. The detailed clinical pictures of the patients with type II citrullinaemia are reported and their outcomes after liver transplantation referred to.

Methods: Ten patients with this disease were evaluated. Seven of them underwent liver transplants using a graft obtained from a healthy family member.

Results: There were six men and four women; the age of onset of encephalopathy ranged from 17 to 51 years. The initial symptom in nine patients was sudden onset disturbance of consciousness, and one patient had long been regarded as having a chronic progressive psychotic illness. High concentrations of plasma citrulline and ammonia were commonly seen on admission. Although brain CT or MRI lacked any consistent findings, the EEG was abnormal in all patients, showing diffuse slow waves. Additionally, in five patients chronic pancreatitis preceded the onset of encephalopathy. After liver transplantation the metabolic abnormalities, including abnormal plasma concentrations of citrulline and ammonia, were immediately corrected and all neuropsychic symptoms soon disappeared, except for impaired cognitive function in one patient. Six out of these seven patients returned to their previous social lives, including work.

Conclusions: The clinical concept of adult onset type II citrullinaemia coincides well with the range of hepatic encephalopathy, and liver transplantation is a very promising therapeutic approach.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Ammonia / blood
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / pathology
  • Brain Edema / diagnosis
  • Brain Edema / etiology
  • Citrulline / blood
  • Citrullinemia / complications*
  • Citrullinemia / diagnosis
  • Citrullinemia / surgery*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology
  • Coma / diagnosis
  • Coma / etiology
  • Consciousness Disorders / diagnosis
  • Consciousness Disorders / etiology*
  • Electroencephalography
  • Female
  • Hepatic Encephalopathy / etiology
  • Hepatic Encephalopathy / surgery
  • Humans
  • Liver Transplantation / methods*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Severity of Illness Index
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Citrulline
  • Ammonia