Clinical application of enzyme immunoassay in the analysis of citrullinemia

Imamura, Yasushi; Kobayashi, Keiko; Yamashita, T; Saheki, Takeyori; Ichiki, Hitoshi; Hashida, Seiichi; Ishikawa, Eiji

doi:10.1016/0009-8981(87)90071-4

Cited by 21 publications

(11 citation statements)

References 12 publications

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“…Later, Saheki et al (1980Saheki et al ( , 1981 reported that the enzyme abnormalities of citrullinemia can be classified as qualitative (type I) or quantitative (type II), and that in type I, ASS is affected not only in the liver but also in the kidney and in cultured fibroblast cells, and is kinetically abnormal, while in type II, ASS is affected only in the liver (Saheki et al 1982(Saheki et al , 1983a, where it is deficient but kinetically normal and has the same specific activity as the control. Further research showed that type I citrullinemia, together with type III, in which ASS is almost completely absent in every cell where the ASS gene is expressed (Saheki et al 1985a(Saheki et al , 1987aImamura et al 1987), is caused by mutations in the ASS gene (Kobayashi et al , 1990(Kobayashi et al , 1991(Kobayashi et al , 1994(Kobayashi et al , 1995aKakinoki et al 1997;Vilaseca et al 2001). Kinetically abnormal mutant ASS is found in patients with type I citrullinemia, and mainly splicing mutations, but not missense mutations, cause type III citrullinemia (Kobayashi et al , 1994(Kobayashi et al , 1995a.…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…SSDI 0014-5793(95)00948-5 ously [2,27]; a high concentration of serum citrulline, a slight increase in serum arginine, an increase in the ratio of threonine to serine in serum, and a decrease in hepatic ASS activity with normal kinetic properties, together with no decrease in renal and/or fibroblast ASS activity. Biochemical data and molecular aspects of the patients (except AP-78 and AP-86) have already been reported [16,17,[19][20][21][23][24][25]27]. The hepatic ASS activities of patients AP-78 and AP-86 were 3.3% and 6% of control, respectively.…”

Section: Patientsmentioning

confidence: 92%

Pancreatic secretory trypsin inhibitor gene is highly expressed in the liver of adult‐onset type II citrullinemia

et al. 1995

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Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS is deficient specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there are no apparent abnormalities in the amount, translational activity, and nucleotide sequence of hepatic ASS mRNA. Recent results of homozygosity testing indicate that the primary defect of type II citrullinemia is not within the ASS gene locus. In this present work, to understand the pathogenesis and pathophysiology of type II citrullinemia, we have characterized the alterations of gene expression in the liver of type II patients using the recently developed mRNA differential display method. Some cDNA bands expressed differently in type 1I citrullinemia patients and control were selected, cloned, and sequenced. Nucleotide sequence analysis and homology searching revealed an interesting clone which has 99% homology with the human pancreatic secretory trypsin inhibitor (hPSTI). Northern blot and RT-PCR analyses showed that the expression of hPSTI mRNA increased significantly in the liver of all type II patients tested. Furthermore, the concentration of hPSTI protein was found to be higher in the liver of type II citrullinemia than in control. These results suggest that hPST! may be related to the primary defect of type II citrullinemia and may be useful as a diagnostic marker, although the detailed mechanism of the high expression of hPSTI mRNA in type 11 liver is not yet known.

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“…We have classified Japanese citrullinemia patients into three types according to enzyme abnormality and into two forms according to pathogenesis (Saheki et al, 1985(Saheki et al, , 1987a(Saheki et al, , 1987bKobayashi et al, 1986Kobayashi et al, , 1987Kobayashi et al, , 1993Kobayashi et al, , 1994Kobayashi et al, , 1995Imamura et al, 1987). One form is adult-onset Type II citrullinemia with a liver-specific ASS deficiency, in which the abnormality is not within the ASS gene locus.…”

Section: Introductionmentioning

confidence: 98%