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)

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

Citrin deficiency initially presents as neonatal intrahepatic cholestasis (NICCD) and often resolves within first year of infancy. Failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) has been recently proposed as a novel post-NICCD phenotype and its clinical features are still being established. Herein, we encountered a 2-year-old girl who was hospitalized for intermittent fever lasting 10 days. Besides pneumonia, we observed an NICCD-like phenotype with the presence of liver dysfunction, dyslipidemia, aminoacidemia, organic academia, and extremely high levels of alpha-fetoprotein (AFP). Genetic testing confirmed the diagnosis of citrin deficiency and, liver histology revealed she had already developed cirrhosis. Although, improvement of biochemical parameters and liver histology were observed after treatment that included dietary restrictions and symptomatic treatments, AFP levels remained elevated (>400 ng/ml) during a 3-year follow-up period. Moreover, liver magnetic resonance imaging (MRI) examination performed on the patient at age 5 revealed the development of multiple liver nodules with diffusion restriction on diffusion-weighted imaging (DWI). These observations highly indicate the possibility of hepatocellular carcinoma (HCC). Thus, this case reveals that an NICCD-like phenotype complicated with cirrhosis can exist during FTTDCD stage without any prior signs. It also emphasizes the necessity of monitoring AFP levels during follow-up for citrin deficiency patients with persistently high AFP level after treatment as FTTDCD may progress to HCC. Individualized treatment strategy for patients with FTTDCD also need to be explored.
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PMID:A Case Report: Can Citrin Deficiency Lead to Hepatocellular Carcinoma in Children? 3162 Apr 7