ARC syndrome with high GGT cholestasis caused by VPS33B mutations.
Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (OMIM 208085) is an autosomal recessive disorder that is caused by mutations in 2 interacting genes VPS33B and VIPAS39. Mutations in VPS33B gene account for most cases of ARC. As low or normal gamma-glutamyl transpeptidase (GGT) activity has been described in all patients with ARC syndrome identified so far, ARC syndrome is a possible diagnosis for low GGT cholestasis. Here we describe a Chinese patient with neonatal cholestasis and a high GGT level in three consecutive tests. She had other typical manifestations of ARC syndrome, including arthrogryposis multiplex congenita, renal involvement and ichthyosis. Genetic study of the VPS33B gene further confirmed the diagnosis by identification of compound heterozygosity of two known disease-causing mutations, c.403+2T > A and c.1509-1510insG. The mechanism of high GGT in this patient is unclear. Nevertheless, this case indicates that ARC syndrome cannot be excluded from the differential diagnosis of neonatal cholestasis even if high GGT activity is found.
Jian-She Wang, Jing Zhao, Li-Ting Li, Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.
Jian-She
JS
Wang
Jian-She Wang, Jing Zhao, Li-Ting Li, Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.
Jing
J
Zhao
Jian-She Wang, Jing Zhao, Li-Ting Li, Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.
Li-Ting
LT
Li
D001176:Arthrogryposis / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002779:Cholestasis / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D051437:Renal Insufficiency / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D015854:Up-Regulation; D033921:Vesicular Transport Proteins / Q000235:genetics*; D005723:gamma-Glutamyltransferase / Q000097:blood*
D015415:Biomarkers; C411584:VPS33B protein, human; D033921:Vesicular Transport Proteins; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human
Arthrogryposis, renal dysfunction and cholestasis syndrome; Cholestasis; Gamma-glutamyl-transpeptidase; Glucosuria; Renal dysfunction; VPS33B