Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020639 (hypoproteinemia)
 1,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe 2 patients with adult-onset type II citrullinemia who developed transient hypoproteinemia and jaundice in early infancy. Liver histology showed a marked fatty change and fibrosis. After the patients had lived without symptoms to the ages of 5 and 16 years, respectively, the diagnosis was made by genetic analysis.
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PMID:Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy. 1134 53

A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.
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PMID:Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. 1554 92

Citrin, encoded by SLC25A13, is a liver-type mitochondrial aspartate-glutamate carrier (AGC), of which deficiency, in autosomal recessive trait, causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). NICCD patients have jaundice, hypoproteinemia, hypoglycemia, galactosemia, growth retardation, fatty liver and multiple aminoacidemia including citrulline, methionine, threonine and tyrosine. Some of the neonates who have experienced NICCD suffer from severe CTLN2 more than 10 years or several decades later. In CTLN2, neuropsychotic symptoms such as disorientation, aberrant behavior, coma and death are observed. Laboratory findings reveal hyperammonemia, citrullinemia, fatty liver and liver-specific decrease in a urea cycle enzyme, argininosuccinate synthetase (ASS). In some cases, hyperlipidemia, pancreatitis and hepatoma are accompanied with CTLN2. Citrin as a liver-type AGC plays a role in supplying aspartate to the cytosol for urea, protein and nucleotide synthesis by exchanging mitochondrial aspartate for cytosolic glutamate and proton, and transporting cytosolic NADH reducing equivalent to mitochondria as a member of malate aspartate shuttle essential for aerobic glycolysis. AGC is also important for gluconeogenesis from lactate. Although it is difficult to explain pathogenesis of the symptoms such as cholestasis in NICCD and liver-specific decrease of ASS protein in CTLN2 from the functions of the AGC, some are understandable by the loss of citrin functions. Many CTLN2 patients have been treated with a low protein and high carbohydrate diet and glycerol at the hyperammonemic coma. We argue that those treatments may result in fatty liver, hyperlipidemia, hyperammonemia and even death due to loss of the citrin functions. Loss of citrin first cause deficiency of aspartate in the cytosol, which results in an increase in cytosolic NADH/NAD(+) ratio and then activation of fatty acid synthesis pathway to compensate the aberrant ratio. This follows inhibition of fatty acid oxidation. The peculiar fondness for food of CTLN2 patients who like protein and dislike carbohydrate and sweets may be related to their metabolic requirements.
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PMID:Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier. 1619 99

Citrin is a liver-type mitochondrial aspartate-glutamate carrier encoded by the SLC25A13 gene, and its deficiency causes adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). Here, the authors investigated clinical findings in Korean infants with NICCD and performed mutation analysis on the SLC25A13 gene. Of 47 patients with neonatal cholestasis, three infants had multiple aminoacidemia (involving citrulline, methionine, and arginine) and galactosemia, and thus were diagnosed as having NICCD. Two of these three showed failure to thrive. The laboratory findings showed hypoproteinemia and hyperammonemia, and liver biopsies revealed micro-macrovesicular fatty liver and cholestasis. The three patients each harbored compound heterozygous 1,638-1,660 dup/ S225X mutation, compound heterozygous 851del4/S225X mutation, and heterozygous 1,638-1,660 dup mutation, respectively. With nutritional manipulation, liver functions were normalized and catch-up growth was achieved. NICCD should be considered in the differential diagnosis of cholestatic jaundice in Korean infants.
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PMID:Neonatal intrahepatic cholestasis caused by citrin deficiency in Korean infants. 1816 5