[Studies on the clinical manifestation and SLC25A13 gene mutation of Chinese patients with neonatal intrahepatic cholestasis caused by citrin deficiency].

Abstract

OBJECTIVE:

To investigate the clinical and laboratory features of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and to characterize the molecular basis and prognosis of this disease.

METHODS:

Twenty-six patients with NICCD were collected because of idiopathic intrahepatic cholestasis and jaundice. The diagnosis was made by routine laboratory data collection, tandem mass spectrometry (MS-MS) and gas chromatography mass spectrometry (GC-MS) analyses. SLC25A13 gene mutation was analyzed by using polymerase chain reaction (PCR), direct DNA sequencing and restriction fragment length polymorphism analyses. The patients were followed up for nearly 2 years.

RESULTS:

The NICCD patients showed low birth weight and the average onset of jaundice was 29 days. Laboratory data showed liver dysfunction, hyperbilirubinemia, hypoproteinemia, high levels of alpha-fetoprotein, prolonged prothrombin time, hypoglycemia and hyperammonemia. MS-MS analysis of the blood samples revealed specific elevation of citrulline, methionine, threonine, tyrosine and elevation of free carnitine, short-chain and long-chain acylcarnitines. GC-MS analysis of the urine samples showed elevated 4-hydroxyl phenyllactic acid and 4-hydroxyl phenylpyruvic acid. Twelve different mutations were identified, including 4 novel mutations, i.e., G386V, R467X, K453R and 1192-1193delT. Forty-four mutated alleles were identified in the 52 alleles (84.6% ). Among them, 851del4, 1638ins23 and IVS6+5G>A mutations were the most frequent mutations, accounting for 40.9%, 20.5% and 11.4% of the total alleles examined respectively. Five of the 26 patients have not been recovered, including 4 died and 1 accepted liver transplantation. No obvious relationship was found between the genotype and phenotype in NICCD.

CONCLUSION:

The 851del4, 1638ins23 and IVS6+5G>A mutations are the hot-spot mutations in Chinese NICCD patients. Some NICCD patients have poor prognosis.

• Authors: Ya-zhi Xing, Wen-juan Qiu, Jun Ye, Lian-shu Han, Shan-shan Xu, Hui-wen Zhang, Xiao-lan Gao, Yu Wang, Xue-fan Gu
• Journal: Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics (Zhonghua Yi Xue Yi Chuan Xue Za Zhi) Vol. 27 Issue 2 Pg. 180-5 (Apr 2010) ISSN: 1003-9406 [Print] China
• PMID: 20376801 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• Mitochondrial Membrane Transport Proteins
• Organic Anion Transporters
• SLC25A13 protein, human
• citrin

Topics

• Base Sequence
• Calcium-Binding Proteins (deficiency)
• Case-Control Studies
• Child, Preschool
• Cholestasis, Intrahepatic (diagnosis, etiology, genetics, therapy)
• DNA Mutational Analysis
• Disease Progression
• Follow-Up Studies
• Genotype
• Humans
• Infant
• Infant, Newborn
• Male
• Mitochondrial Membrane Transport Proteins (genetics)
• Mutation
• Organic Anion Transporters (deficiency)
• Prognosis