Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients.
A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.
Tazawa
Yusaku
Y
Department of Pediatrics, Miyagi South Medical Center Hospital, Oogawara, Japan.
Kobayashi
Keiko
K
Abukawa
Daiki
D
Nagata
Ikuo
I
Maisawa
Shunichi
S
Sumazaki
Ryo
R
Iizuka
Toshiyuki
T
Hosoda
Yoshito
Y
Okamoto
Manabu
M
Murakami
Jun
J
Kaji
Shunsaku
S
Tabata
Ayako
A
Lu
Yao Bang
YB
Sakamoto
Osamu
O
Matsui
Akira
A
Kanzaki
Susumu
S
Takada
Goro
G
Saheki
Takeyori
T
Iinuma
Kazuie
K
Ohura
Toshihiro
T
D000596:Amino Acids / Q000097:blood; D000743:Anemia, Hemolytic / Q000150:complications / Q000473:pathology; D001647:Bile Acids and Salts / Q000097:blood; D001656:Biliary Atresia / Q000150:complications / Q000469:parasitology; D001779:Blood Coagulation Factors; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D002780:Cholestasis, Intrahepatic / Q000150:complications / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology*; D020159:Citrullinemia / Q000150:complications / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D005526:Food, Formulated; D005690:Galactose / Q000097:blood; D006505:Hepatitis / Q000150:complications / Q000473:pathology; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000473:pathology; D007019:Hypoproteinemia / Q000150:complications / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics*; D027361:Organic Anion Transporters / Q000172:deficiency*; D020176:Tyrosinemias / Q000150:complications / Q000473:pathology; D014815:Vitamins / Q000627:therapeutic use
D000596:Amino Acids; D001647:Bile Acids and Salts; D001779:Blood Coagulation Factors; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; D014815:Vitamins; C008822:citrin; D005690:Galactose