Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type II citrullinemia (CTLN2) is characterized by a deficiency of argininosuccinate synthetase (ASS) in the liver. Mutation analysis of the SLC25A13 gene, which is responsible for CTLN2, provides a rapid and accurate diagnosis. We describe clinical, biochemical and histologic features of two patients, whose diagnosis was finally made by mutation analysis. They initially presented with symptoms related to hyperammonemia at 16 to 22 years of age. A patient had shown mental retardation and growth failure from early childhood. Laboratory findings including amino acids, were characteristic, such as elevated citrulline, arginine, and lysine concentrations, but definitive diagnosis had not been made. The patients died of liver cirrhosis and hepatoma at 31 and 34 years old, respectively. Fatty change in the hepatocytes was commonly observed in the autopsied specimens. ASS activity was decreased in the liver of both patients, and a concomitant decrease of arginase activity was found in one case. Investigation for the SLC25A13 mutation revealed that one patient was homozygous for IVS11 + 1G>A, and the other was compound heterozygote (851del4/S225X). Comparison of genetic, enzymatic and biochemical data among various cases of CTLN2 will be essential to understand the real nature of the disease.
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PMID:Application of mutation analysis for the previously uncertain cases of adult-onset type II citrullinemia (CTLN2) and their clinical profiles. 1251 93

Citrullinemia is a metabolic disorder characterized by elevated plasma concentrations of citrulline and ammonia. Adult-onset citrullinemia (type II, CTLN2) has been attributed to citrin deficiency caused by mutations in the SLC25A13 gene. CTLN2 is associated with a high incidence of hepatocellular carcinoma (HCC) in Japanese. We report a 48-year-old Taiwanese man with citrullinemia, who was in good health until the age of 34 when he had repeated episodes of consciousness disturbance. Hyperammonia (201 micromol/L) was found during an episode of coma. Liver function and electrolyte levels were normal at that time. Serologic markers of viral hepatitis B and C were negative. Analysis of genomic DNA extracted from peripheral blood leukocytes showed homozygous 851del4 mutation in exon 9 of the SLC25A13 gene on chromosome 7q21.3. Fourteen years after disease onset, at the age of 48, he was admitted due to an episode of coma. Abdominal sonography and computed tomography showed a 2.5 cm tumor in the left lobe of the liver, without evidence of liver cirrhosis. Wedge resection of the tumor was performed and grade 2 HCC was diagnosed. The nontumor part of the resected specimen showed chronic persistent hepatitis with moderate steatosis. The results in this case support that both citrin deficiency and steatohepatitis may contribute to hepatocarcinogenesis.
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PMID:Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset citrullinemia complicated with steatosis and hepatocellular carcinoma. 1700 Apr 60

Citrin deficiency (CD) is an autosomal recessive disorder with SLC25A13 as causative gene that encodes citrin, the liver-type aspartate/glutamate carrier isoform 2 (AGC2). Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), the major CD phenotype at pediatric age, has been previously reported as a self-limiting condition with clinical presentations resolving between 6 months and 1 year of life. We report the prenatal diagnosis of CD in a family with a fatal NICCD proband. The proband was a 10-month-old male presenting cough for 8 days and jaundiced skin 1 day. Physical examination revealed fever, dark jaundiced sclera and skin, hoarse breathing sounds, and hepatosplenomegaly. Laboratory tests uncovered elevated cholestatic indices, increased ammonia, and prolonged activated partial thromboplastin time and prothrombin time, and reduced fibrinogen. Sonography showed the features of liver cirrhosis. Metabolome analysis uncovered large quantity of 4-hydroxyphenyllactate and dicarboxylates in urine and increased citrulline and methionine in blood. The patient passed away due to liver failure at his age of 13.5 months. Mutation analysis revealed him a homozygote of 851del4, a four-base deletion in exon 9 of SLC25A13 gene. On request of the parents who had a second fetus, prenatal diagnosis of CD was performed by PCR-electrophoresis following amniocentesis and amniocyte culture, and demonstrated the fetus a carrier of the same mutation. The fatal proband in the present report has provided clinical evidence challenging the traditional concept on NICCD prognosis. Moreover, as the first trial on CD prenatal diagnosis, this study might open a novel area for clinical management of CD.
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PMID:Prenatal diagnosis of citrin deficiency in a Chinese family with a fatal proband. 2209 53

Infantile liver failure syndrome type 1 (ILFS1) is a Mendelian disease due to biallelic mutations in the cytoplasmic leucyl-tRNA synthetase gene (LARS). This study aimed to report the clinical and molecular features of the first non-caucasian ILFS1 patient, providing reliable evidences for the definite diagnosis of ILFS1. The 2 years and 9 months old male patient was referred to the hospital with hepatosplenomegaly over 1 year. At age 17 months, he was found to have hepatosplenomegaly and anemia. Since then, he had been managed in different hospitals. The laboratory tests showed liver dysfunction, hypoproteinemia, coagulopathy and anemia, along with histologically-confirmed cirrhosis and fatty liver; however, the etiology remained undetermined. The subsequent SLC25A13 mutation analysis by means of prevalent mutation screening and Sanger sequencing only revealed a paternally-inherited mutation c.1658G>A, and no aberrant SLC25A13 transcripts could be detected from the maternal allele on cDNA cloning analysis, ruling out the possibility of citrin deficiency. Further target exome high-throughout sequencing of genes relevant to genetic liver diseases detected a paternal c.2133_2135del (p.L712del) and a maternal c.1183G>A (p.D395N) mutation in LARS gene. This finding was then confirmed by Sanger sequencing, and ILFS1 was thus definitely diagnosed. The child has been followed up till age 4 years, and his condition became stabilized.
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PMID:[Clinical feature and molecular diagnostic analysis of the first non-caucasian child with infantile liver failure syndrome type 1]. 2877 68