Citrullinuria a New Aminoaciduria Associated With Mental Retardation

McMurray, W. C.; Mohyuddin, Fazl; Rossiter, R. J.; Rathbun, J. C.; Valentine, G. H.; Koegler, S.J.; Zarfas, Donald E.

doi:10.1016/s0140-6736(62)91135-2

Cited by 109 publications

(31 citation statements)

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“…Key Words: citrullinemia, argininosuccinate synthetase, serum amino acids, citrulline, arginine Citrullinemia, first described by McMurray et al [1], is a rare hereditary disorder caused by deficient activity of argininosuccinate synthetase (ASS). In Japan, however, many cases of citrullinemia distinct from the classical neonatalonset type described by McMurray et al have been found, and they have some unique characteristics concerning the clinical picture, enzyme abnormalities, and so on [2][3][4] ; for example, the disease has been found in adults suffering from disturbances of consciousness.…”

Section: Discussionmentioning

confidence: 99%

Serum Amino Acid Pattern of Type II Citrullinemic Patients and Effect of Oral Administration of Citrulline

Saheki

Kobayashi

Miura

et al. 1986

J. Clin. Biochem. Nutr.

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SummaryTwenty-four cases of type II citrullinemia, diagnosed as such based on enzymatic analysis showing a decreased enzyme content of kinetically-normal argininosuccinate synthetase in the liver, showed the following features of their serum amino acid patterns : 1) Serum arginine levels were higher than in controls and were significantly correlated with serum citrulline levels. 2) Serum alanine, serine, glycine, and branchedchain amino acids (valine + isoleucine + leucine) were significantly lower than in the controls, while threonine was rather higher and aromatic amino acids (tyrosine + phenylalanine) remained at the control level. Thus the ratio of threonine to serine and of branched-chain amino acids to aromatic amino acids were characteristically higher and lower than the control values, respectively.The above characteristics were quite unique to type II citrullinemia and not found in serum amino acid patterns of type I and III citrullinemic patients. Examination of effect of oral administration of citrulline

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Section: Discussionmentioning

confidence: 99%

Serum Amino Acid Pattern of Type II Citrullinemic Patients and Effect of Oral Administration of Citrulline

Saheki

Kobayashi

Miura

et al. 1986

J. Clin. Biochem. Nutr.

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“…Citrullinemia was first described by McMurray et al (1962). Since then, many neonatal and infantile cases have been reported.…”

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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“…Only 3 cases have been reported previously (McMurray et al, 1962;1963;McMurray et al, 1964;Mohyuddin, Rathbun, and McMurray, 1967;Morrow, Barness, and Efron, 1967;Morrow, 1967;Wick, Brechbuhler, and Girard, 1970). The normal synthesis of argininosuccinic acid is blocked in this disease due to a deficiency of argininosuccinate synthetase, which has been demonstrated in liver cells and fibroblasts (McMurray et al, 1964;Tedesco and Mellman, 1967). The clinical symptoms are periodic vomiting and irritability, convulsions, and mental retardation.…”

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confidence: 99%