Genotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center.

Citrin is a liver-type aspartate/glutamate carrier (AGC) encoded by the gene SLC25A13. Two phenotypes for human citrin deficiency have been described, namely the adult-onset citrullinemia type II (CTLN2) and the neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). However, citrin deficiency currently remains a perplexing and poorly recognized disorder. In particular, description of post-NICCD clinical presentations before CTLN2 onset is rather limited. Analysis of SLC25A13 mutations, identification of dysmorphic erythrocytes, hepatobiliary scintigraphic imaging and investigation of post-NICCD clinical presentations were performed in a citrin-deficient cohort comprised of 51 cases of children diagnosed with citrin deficiency in a Chinese pediatric center. Twelve SLC25A13 mutations were detected in this cohort, including the novel V411M and G283X mutations. Among the 51 citrin-deficient subjects, 7 cases had echinocytosis, which was associated with more severe biochemical abnormalities. Delayed hepatic discharge and bile duct/bowel visualization were common scintigraphic findings. Moreover, 9 of the 34 post-NICCD cases demonstrated concurrent failure to thrive and dyslipidemia, constituting a clinical phenotype different from NICCD and CTLN2. The novel mutations, echinocytosis, hepatobiliary scintigraphic features and the novel clinical phenotype in this study expanded the genotypic and phenotypic spectrum of citrin deficiency, and challenge the traditionally-assumed 'apparently healthy' period after the NICCD state for this disease entity.

Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings.

Conventional MR, diffusion-weighted, and diffusion tensor imaging were performed in an 8-day-old girl with citrullinemia. She had severe hyperammonemia for several days. On conventional T2-weighted MR images, symmetric, confluent high signal intensity was found in the bilateral thalami, basal ganglia, cortex, and subcortical white matter. Diffusion-weighted imaging demonstrated decreased apparent diffusion coefficient in these areas, reflecting cytotoxic edema. Follow-up MR imaging at the age of 4 months revealed subcortical cysts, ulegyric changes, and atrophy, which were most prominent in the occipital lobes. Diffusion tensor imaging revealed decreased anisotropy throughout the brain, consistent with diffuse injury to the oligodendro-axonal unit. Diffusion-weighted and diffusion tensor imaging are valuable techniques for the detection of irreversible brain damage and for the characterization of hyperintense lesions on T2-weighted MR images in patients with the neonatal form of citrullinemia.

CT findings in the infantile form of citrullinemia.

Citrullinemia is a rare autosomal recessive inborn error of the urea cycle due to a deficiency in argininosuccinic acid synthetase. We present two cases of the infantile form of citrullinemia in which CT revealed bilateral and symmetric corticosubcortical hypoattenuating areas, ulegyric changes, and atrophy in the frontal lobes, as well as atrophy in the gyrus cinguli, insulae, and temporal lobes.