| Project/Area Number |
16591005
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
OHURA Toshihiro Tohoku University, Department of Pediatrics, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10176828)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Keiko Tohoku University, Department of Molecular Metabolism and Biochemical Genetics, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (70108869)
KURE Shigeo Tohoku University, Department of Medical Genetics, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10205221)
SAKAMOTO Osamu Tohoku University, Department of Pediatrics, Hospital, Instructor, 病院・助手 (20333809)
KONDO Yoshiaki Tohoku University, Department of Medical Informatics, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00221250)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | citrin / citrullinemia / SLC25A13 / Newborn screening / neonatal intrahepatic cholestasis / NICCD / シトリン欠損症 / ガラクトース血症 |
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| Research Abstract |
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) was discovered in infants having intrahepatic cholestasis with fatty liver, but their long term outcome is not clear. To clarify the clinical features of NICCD, we sent a detailed questionnaire to pediatricians in charge of patients with NICCD and collected data from 69 patients. Among these patients, we retrospectively reviewed symptoms, management and long term outcomes of 27 of them, who were referred to hospitals because of positive results from newborn screening.
Of these 27 patients, hypergalactosemia was detected in 17 patients, hypermethioninemia in 16, and hyperphenylalaninemia in 6. It was also observed that ten patients were positive for both methionine and galactose, one was positive for both methionine and phenylalanine and surprisingly one patient was positive for methionine, galactose and phenylalanine at the same time. The laboratory data obtained from the patients were similar and suggested severe cholestasis and liver damage. Serum levels of conjugated bilirubin, γ-GTP activity, total bile acid and galactose were high. Total protein and vitamin K dependent coagulation factors were low. Blood ammonia levels were only mildly elevated. The most characteristic features of NICCD are the abnormal amino acid patterns. Serum amino acid analyses showed a significant elevation of citrulline and methionine. The concentration of threonine, tyrosine, lysine and arginine were also 2-4 times higher than the control levels. We speculate that some of the NICCD patients may develop CTLN2 with neuropsychiatic symptoms several decades from now. It is now important and urgent to find the genetic or environmental factors which lead to the deterioration to CTLN2. We have to continue to observe these patients regularly to see whether they develop symptoms of CTLN2.
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