• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.35-41
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• 2012

Since the causative gene, SLC25A13 which encodes citrin, was discovered in 1999, over 500 cases with citrin deficiency have been identified. Two phenotypes can occur by citrin deficiency, neonatal intrahepatic cholestasis by citrin deficiency (NICCD) and adult-onset type II citrullinemia (CTLN2). Some patients with NICCD develop CTLN2 in their later lives. Although cholestatic jaundice is spontaneously resolved within the first year of life in most cases with NICCD, a few cases experience progressive hepatic failure. In this report, two neonates with severe type of NICCD were described. Both cases exhibited neonatal cholestatic jaundice, hyperammonemia and severe coagulopathy. Of note, plasma citrulline and blood galactose levels were extremely high. Serum ${\alpha}$-fetoprotein, plasma methionine, arginine, and threonine-to-serine ratio were elevated as well. SLC25A13 mutations were found in all the four alleles of both patients. With the commencement of lactose-free formula, coagulopathy and hyperammonemia were resolved, and galactose level was normalized. Currently, no factor has been identified to predict the prognosis of NICCD. More experiences are needed to build up the adequate therapeutic strategies for severe type of NICCD. Our experience, however, indicates that the degree of citrullinemia and galactosemia might reflect the severity.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.186-190
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• 2014

Citrullinemia type 2 (citrin deficiency) is an autosomal recessive inborn error metabolism, caused by the SLC25A13 gene mutation. Citrin deficiency is associated with two clinical phenotype; neonatal-onset type II citrullinemia (CTLN2), also known as neonatal intraphepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset CTLN2. Clinical manifestations of NICCD include poor growth, intrahepatic cholestasis, liver dysfunction and increased plasma citrulline, methionine, threonine, arginine. The molecular diagnosis could be confirmed by SLC25A13 gene mutation analysis. A 3-month-old male infant with persistent jaundice was referred for evaluation. Newborn screening was normal at birth. Mild elevation of serum ammonia and AST/ALT were observed. Plasma amino acid analysis showed significantly elevated citrulline, methionine, threonine. DNA sequence analysis of the SLC25A13 gene revealed two compound heterozygous mutations, c.[852_855del]($p.Met285Profs^*2$) and [1180+1G>A]. We suggest that NICCD should be considered as one of the cause of in infants with cholestatic jaundice, although the newborn screening was normal.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.155-159
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• 2015

Citrin deficiency (OMIN #605814) is an autosomal recessive disorder caused by the SLC25A13 gene mutation with abnormal biochemical findings, including increased serum ammonia, citrulline, arginine, galactose, serum threonine-to-serine ratio, serum pancreatic secretory trypsin inhibitor, and alpha-fetoprotein. Citrin deficiency can manifest in three ways: in newborns as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as citrullinemia type 2 (CTLN2) with recurrent hyperammonemia and neuropsychiatric symptoms. We report a 35-day-old asymptomatic patient with citrin deficiency who had abnormal biochemical findings.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.96-107
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• 2006

Citrin deficiency resulting from mutations of SLC25A13is associated with two major clinical phenotypes; neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type 2 citrullinemia (CTLN2). In Korea, 7 cases of citrin deficiency have been diagnosed based on biochemical and molecular findings. Four NICCD cases were identified by newborn screening using MS/MS or presenting symptoms like cholestatic jaundice. They are all males, presenting with conjugated hyperbilirubinemia, elevated liver enzymes, hypoalbuminemia, mild hyperammonemia, elevated citrullin, methionine and threonine. All of them have been spontaneously recovered from hepatic manifestation by the age of 6-8 months. Mutation analysis has been performed using their genomic & cDNAs obtained from skin fibroblasts. They turned out to be compound heterozygotes carrying each of 851del4, IVS11+1G>A, and IVS13+1G>A. Three CTLN2 patients were identified. Two adult male patients presented with a sudden loss of consciousness, seizure, vomiting, hyperammonemia and citrullinemia in their twenties. They carried an IVS13+1G>A, 851del4, and IVS11+1G>A mutant alleles. The other CTLN2 patient was 52 year old female patient, manifesting lethargy, altered consciousness, irritability and hyperammonemia. Similar clinical symptoms had recurred at the delivery of first and second babies in her past medical history. She was managed by hemodialysis and survived with neurological sequellae. Also, we screened the presence of 9 common mutations in 500 Korean newborns using dried blood spot of filter papers. Only a allele carried 854del4 mutation. In conclusion, the entire picture of citrin deficiency in Korea including incidence, genotype, clinical features and natural courses, is still vague at the present time.