Living-Related Liver Transplantation for Type Ii Citrullinemia Using a Graft From Heterozygote Donor1

Kasahara, Mureo; Ohwada, Susumu; Takeichi, Takayuki; Kaneko, Hiroaki; Tomomasa, Takeshi; Morikawa, Akihiro; Yonemura, Keiichi; Asonuma, Katsuhiro; Tanaka, Kōichi; Kobayashi, Keiko; Saheki, Takeyori; Takeyoshi, Izumi; Morishita, Yasuo

doi:10.1097/00007890-200101150-00027

Cited by 51 publications

(44 citation statements)

References 9 publications

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“…Patients diagnosed were from 11 to 79 years old with a mean age of 34.4 Ϯ 12.6 (n ϭ 102) Yasuda et al 2000). Although the prognosis is bad, liver transplantation is remarkably effective (Todo et al 1992;Yazaki et al 1996;Kawamoto et al 1997;Onuki et al 2000;Takenaka et al 2000;Kasahara et al 2001;Ikeda et al 2001). Symptoms are often provoked after medication, infection, or alcohol intake.…”

Section: Clinical Features Of Ctln2mentioning

confidence: 99%

“…On the other hand, liver transplantation has been shown to be very effective. Following two cases of orthotopic liver transplantation performed at Pittsburgh in 1988 (Todo et al 1992) and at Brisbane in 1993 (Kawamoto et al 1997), 20 cases of CTLN2 in Japan have been treated with livingrelated partial liver transplantation (Yazaki et al 1996;Onuki et al 2000;Takenaka et al 2000;Kasahara et al 2001;Ikeda et al 2001). Liver transplantation normalizes most of the metabolic disturbances and symptoms, except those from brain atrophy already occurred.…”

Section: Ctln2 and Niccd As A Citrin Deficiencymentioning

confidence: 99%

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Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)

2002

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Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD) Abstract By using homozygosity mapping and positional cloning, we have shown that adult-onset type II citrullinemia (CTLN2) is caused by mutations of the SLC25A13 gene, which is localized on chromosome 7q21.3 and encodes a mitochondrial solute carrier protein named citrin. So far, we have reported nine mutations, most of which cause loss of citrin, and we have established several methods for DNA diagnosis. These methods have shown that more than 90% of the patients diagnosed as suffering from CTLN2 by enzymatic analysis carry SLC25A13 mutations in both alleles, indicating that CTLN2 is caused by citrin deficiency. Furthermore, by using the same DNA diagnosis methods, we discovered that 70 neonates or infants suffering from a particular type of neonatal hepatitis carry the same SLC25A13 mutations. Since the symptoms of the neonates are different from those of the more severe CTLN2 and usually ameliorate without special treatment, we designated the neonatal disease neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). We conclude that citrin deficiency causes NICCD in neonates and CTLN2 in adults through the additional effects of genetic or environmental modifiers. Since the function of citrin, together with that of an isoform, aralar, was found to be as a mitochondrial aspartate glutamate carrier, the various symptoms of NICCD and CTLN2 may be understood as caused by defective aspartate export from the mitochondria to the cytosol and defects in the malate aspartate shuttle. It is, however, still difficult to understand the cause of the hepatic deficiency of argininosuccinate synthetase protein in CTLN2.Received

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Section: Clinical Features Of Ctln2mentioning

confidence: 99%

Section: Ctln2 and Niccd As A Citrin Deficiencymentioning

confidence: 99%

Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)

2002

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“…For CTLN2 patients with poor prognosis and high mortality, there is no effective treatment at the present except liver transplantation (Ikeda et al 2001;Kasahara et al 2001;Yazaki et al 2004). On the other hand, NICCD shows multiple metabolic abnormalities, including an aminoacidemia (involving citrulline, threonine, methionine, tyrosine, and arginine), galactosemia, hypoproteinemia, hypoglycemia, cholestasis, and fatty liver Ohura et al 2003;Tazawa et al 2004;Hachisu et al 2005).…”

Section: Introductionmentioning

confidence: 99%

“…A few NICCD patients, however, have a severe form of the disorder with liver damage associated with tyrosinemia and require liver transplantation (Tamamori et al 2002). Some neonatal NICCD patients develop severe CTLN2 more than a decade or several decades later (Kasahara et al 2001;Tomomasa et al 2001;Saheki and Kobayashi 2002).…”

Section: Introductionmentioning

confidence: 99%

Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency

et al. 2005

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Deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier (AGC), encoded by the SLC25A13 gene on chromosome 7q21.3, causes autosomal recessive disorders: adult-onset type II citrullinemia (CTLN2) and neonatal hepatitis associated with intrahepatic cholestasis (NICCD). So far, we have described 12 SLC25A13 mutations: 11 were from Japan and one from Israel. Three mutations found in Chinese and Vietnamese patients were the same as those in Japanese patients. In the present study, we identified a novel mutation IVS6+1G>C in a Japanese CTLN2 patient and widely screened 12 SLC25A13 mutations found in Japanese patients in control individuals from East Asia to confirm our preliminary results that the carrier frequency was high in Asian populations. Mutations 851-854del and 1638-1660dup were found in all Asian countries tested, and 851-854del associated with 290-haplotype in microsatellite marker D7S1812 was especially frequent. Other mutations frequently detected were IVS11+1G>A in Japanese and Korean, S225X in Japanese, and IVS6+5G>A in Chinese populations. We found a remarkable difference in carrier rates in China (including Taiwan) between north (1/ 940) and south (1/48) of the Yangtze River. We detected many carriers in Chinese (64/4169 = 1/65), Japanese (20/1372 = 1/69) and Korean (22/2455 = 1/112) populations, suggesting that over 80,000 East Asians are homozygotes with two mutated SLC25A13 alleles.

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“…Information on the natural history of the disease during this adaptation period is, however, scanty. Much later in life, some of these NICCD patients may develop CTLN2 (12,13). Thus, some type of adaptation or compensation improves the symptoms in childhood and adolescence (14).…”

Section: Discussionmentioning

confidence: 99%

Six cases of citrin deficiency in Korea

Kim

et al. 2007

Int J Mol Med

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Abstract. Citrin deficiency resulting from mutations of the SLC25A13 gene is associated with two major clinical phenotypes; neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type 2 citrullinemia (CTLN2). In Korea, 6 cases of citrin deficiency were diagnosed based on biochemical and molecular findings. Four NICCD patients (2 boys and 2 girls) presented high citrulline levels on a newborn screening test or neonatal cholestasis. They were associated with conjugated hyperbilirubinemia, elevated liver enzymes, hypoalbuminemia, mild hyperammonemia, elevated citrulline, methionine and threonine. All of the hepatic manifestations were resolved spontaneously at the age of 5-9 months. Mutation analysis identified them as compound heterozygotes carrying each of the c.851del4, IVS11+1G>A, IVS13+1G>A, G393S, and IVS16ins3kb mutant alleles. Two adult male CTLN2 patients were identified. They were aged 24 and 37 years, and presented sudden loss of consciousness, hyperammonemia and citrullinemia. They were compound heterozygotes with IVS13+1G>A and IVS16ins3kb, and with c.851del4 and IVS11+1G>A mutant alleles. This report describes the clinical characteristics, biochemical findings and molecular analysis of the SLC25A13 gene of patients with citrin deficiency in Korea.

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Living-Related Liver Transplantation for Type Ii Citrullinemia Using a Graft From Heterozygote Donor1

Abstract: Living-related liver transplantation using a graft from genetically proven heterozygote donors might be a permissible treatment modality for CTLN2. Long-term observation may be necessary to make a definite conclusion possible.

Cited by 51 publications

References 9 publications

Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)

Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)

Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency

Six cases of citrin deficiency in Korea

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