title: Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients.
abstract: 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.
authors.affiliation: Department of Pediatrics, Miyagi South Medical Center Hospital, Oogawara, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Tazawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Daiki
authors.initials: D
authors.lastname: Abukawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nagata
authors.forename: Shunichi
authors.initials: S
authors.lastname: Maisawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Sumazaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Iizuka
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Hosoda
authors.forename: Manabu
authors.initials: M
authors.lastname: Okamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Murakami
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Kaji
authors.forename: Ayako
authors.initials: A
authors.lastname: Tabata
authors.forename: Yao Bang
authors.initials: YB
authors.lastname: Lu
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Matsui
authors.forename: Susumu
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Goro
authors.initials: G
authors.lastname: Takada
authors.forename: Takeyori
authors.initials: T
authors.lastname: Saheki
authors.forename: Kazuie
authors.initials: K
authors.lastname: Iinuma
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
mesh_terms: 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
chemical_list: 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