Published online Apr 28, 2014. doi: 10.3748/wjg.v20.i16.4830
Revised: February 9, 2014
Accepted: March 5, 2014
Published online: April 28, 2014
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.
Core tip: Neonatal cholestasis with low or normal gamma glutamyl transpeptidase (GGT) activity was regarded as a characteristic feature of arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Here we describe a patient who presented with neonatal cholestasis and high GGT activities. She had all other typical clinical manifestations of ARC syndrome. The diagnosis was finally confirmed by the presence of compound heterozygosity of two known VPS33B disease-causing mutations. Our case indicates that ARC syndrome cannot be excluded in neonatal cholestasis even with unexpected high GGT activity.