AB089. Postnatal and prenatal diagnosis for neonatal intrahepatic cholestasis caused by citrin deficiency

Background and objective: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) which resulted from mutation in SLC25A13 gene can present transient intrahepatic cholestasis, low birth weight, growth retardation, hypoproteinemia, prolong jaundice, chronic liver disease and so on. This study aimed to identify mutations of SLC25A13 for 649 NICCD and 46 siblings, from September 2009 to December 2014 and prenatal diagnosis for pregnancies with high risk of NICCD.

Methods: Detection four common termed as 851del4, IVS6 + 5G > A, 1638ins23, IVS16ins3kb for NICCD patients by DNA analysis (PCR-RFLP) and confirm by directly sequencing. The NICCD parents who had fetus then enrolled in DNA testing for the carrier. Prenatal diagnosis for their fetus was performed by PCR-RFLP following by amniocentesis and amniocyte culture.

Results: In 695 patients, 169 (24.3%) patients have identified mutations, of which 93 patients were 851del4 homozygote, 62 patients were 851del4 heterozygote, three patients were heterozygote of single mutation 1638ins23, one patient was heterozygote of single mutation IVS6 + 5G > A and two patients were compound heterozygote of 1638ins23 + 851del4, two patients were compound heterozygote (851del4 + IVS6 + 5G > A), six patients were compound heterozygote of (851del4 + IVS16ins3kb); 851del4 was the major mutation type, accounting for 76.3% in mutant allele, followed by c.1638ins23 (1.5%), IVS16ins3kb (1.8%), and IVS6 + 5G > A (0.9%); out of 10 couple enrolled DNA testing, two fathers revealed that they were homozygous mutation without any clinical figure and the others were carrier. Among four pregnancies having prenatal diagnosis, two fetuses were homozygote, one fetu was heterozygote and the remaining was normal.

Conclusions: 851del4 was the most common mutation in Vietnamese NICCD patients. Moreover, citrin deficiency prenatal diagnosis might open a novel area of clinical management for citrin deficiency in Vietnam.

Keywords: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD); SLC25A13 gene; mutation; DNA analysis; citrin deficiency; Vietnam