RESUMO
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.