Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 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

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