Chubby Face and the Biochemical Parameters for the Early Diagnosis of Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency

ABSTRACT Objectives: To identify facial and biochemical characteristics as early clinical features of neonatal intrahepatic cholestasis due to citrin deficiency (NICCD). Patients and Methods: Ten patients with diagnoses of NICCD by SLC25A13 mutation analysis in Taiwan were recruited. A “Chubby Index” was developed for objective measurement of their facial characteristics. Liver function profiles were analyzed and compared with data on neonatal hepatitis and biliary atresia. Results: Chubby face was observed in early infancy in all 5 patients whose serial photographs were taken. A significant difference in the Chubby Index was seen between NICCD infants and healthy infants (1.331 ± 0.07 vs 1.068 ± 0.059; P < 0.05). NICCD is characterized by an aspartate aminotransferase–to–alanine aminotransferase ratio of 2 or greater, a direct bilirubin–to–total bilirubin ratio under 0.67, and a standard deviation score for α‐fetoprotein of 4 or greater, with respect to neonatal hepatitis and biliary atresia. Although chubby face, abnormal liver function profiles, and multiple amino acidemia gradually disappeared after age 1 year, an increase in hepatic echogenicity was observed in most patients in long‐term follow‐up. Conclusions: Our Chubby Index is an informative measurement of the facial characteristics of infants with NICCD. The chubby face features, along with an aspartate aminotransferase–to–alanine aminotransferase ratio of 2 or greater, a direct bilirubin–to–total bilirubin ratio under 0.67, and a standard deviation score for α‐fetoprotein of 4 or greater, may serve as useful clinical indicators for diagnosing NICCD early in infancy.