Effects of citrin deficiency in the perinatal period: feasibility of newborn mass screening for citrin deficiency.

Abstract

Deficiency of citrin due to mutations of the SLC25A13 gene causes adult-onset type II citrullinemia (CTLN2) and one type of neonatal intrahepatic cholestasis (NICCD). About half of the NICCD patients are detected based on high galactose, phenylalanine, and/or methionine concentrations on newborn mass screening (NMS). To clarify the perinatal and neonatal effects and the inconsistent results on NMS, we examined aminograms, the levels of bile acids and galactose in dried blood spots for NMS from 20 patients with NICCD. Birth weight was low for gestational age (-1.4 +/- 0.7 SD). Affected fetuses may have suffered intrauterine citrin deficiency. The first abnormality detected after birth was citrullinemia, and 19 of 20 patients had citrulline levels higher than +2 SD of controls. Tyrosine, phenylalanine, methionine, galactose, and bile acids were less affected than citrulline on d 5 after birth. Galactose and bile acids levels were increased at 1 mo in comparison with d 5 after birth due to impairment of the cytosolic NADH reducing-equivalent supply into mitochondria of hepatocytes. Patients with negative findings on NMS had low levels of total 20 amino acids. Citrulline/serine, citrulline /leucine plus isoleucine, and citrulline/total amino acids ratios, controlled for the confounding effect of low amount of total amino acids, were higher in all patients than +2 SD, +2 SD, and +3 SD of controls, respectively. NMS for citrin deficiency (frequency of homozygote with SLC25A13 mutation: 1/10,000-1/38,000 in East Asia) will be useful for clarification of the clinical course, treatment, and prevention of this disease.

• Authors: Akiko Tamamori, Akie Fujimoto, Yoshiyuki Okano, Keiko Kobayashi, Takeyori Saheki, Yasuko Tagami, Hazime Takei, Yosuke Shigematsu, Ikue Hata, Hajime Ozaki, Daisuke Tokuhara, Yutaka Nishimura, Tohru Yorifuji, Noboru Igarashi, Toshihiro Ohura, Takashi Shimizu, Koji Inui, Norio Sakai, Daiki Abukawa, Takayuki Miyakawa, Mika Matsumori, Kyoko Ban, Hiroaki Kaneko, Tsunekazu Yamano
• Journal: Pediatric research (Pediatr Res) Vol. 56 Issue 4 Pg. 608-14 (Oct 2004) ISSN: 0031-3998 [Print] United States
• PMID: 15295082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Bile Acids and Salts
• Membrane Transport Proteins
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Proteins
• SLC25A13 protein, human
• Galactose

Topics

• Amino Acids (blood)
• Bile Acids and Salts (blood)
• Cholestasis, Intrahepatic (diagnosis, genetics)
• Citrullinemia (diagnosis, genetics)
• Feasibility Studies
• Female
• Galactose (blood)
• Humans
• Infant, Newborn
• Male
• Membrane Transport Proteins (deficiency, genetics)
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Proteins (deficiency, genetics)
• Neonatal Screening (methods)