Chubby face and the biochemical parameters for the early diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency.
OBJECTIVE
To identify facial and biochemical characteristics as early clinical features of neonatal intrahepatic cholestasis due to citrin deficiency (NICCD).


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 alpha-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 alpha-fetoprotein of 4 or greater, may serve as useful clinical indicators for diagnosing NICCD early in infancy.
Chen
Hung-Wen
HW
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Chen
Huey-Ling
HL
Ni
Yen-Hsuan
YH
Lee
Ni-Chung
NC
Chien
Yin-Hsiu
YH
Hwu
Wuh-Liang
WL
Huang
Yuan-Te
YT
Chiu
Pao-Chin
PC
Chang
Mei-Hwei
MH
D044466:Asian People / Q000235:genetics; D001663:Bilirubin / Q000032:analysis; D001774:Blood Chemical Analysis / Q000379:methods*; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D016022:Case-Control Studies; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003937:Diagnosis, Differential; D005145:Face / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008111:Liver Function Tests; D008297:Male; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009154:Mutation / Q000235:genetics; D027361:Organic Anion Transporters / Q000172:deficiency*; D013624:Taiwan / Q000453:epidemiology; D000509:alpha-Fetoproteins / Q000032:analysis
D002135:Calcium-Binding Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; D000509:alpha-Fetoproteins; C008822:citrin; D001663:Bilirubin