HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Clinical characteristics and VPS33B mutations in patients with ARC syndrome.

AbstractOBJECTIVES:
ARC (arthrogryposis, renal dysfunction, and cholestasis) syndrome is a rare, fatal cause of neonatal intrahepatic cholestasis without known treatment modalities and has recently been ascribed to a mutation in the VPS33B gene. We assessed the clinical characteristics and investigated the VPS33B mutations in Korean patients with ARC syndrome.
PATIENTS AND METHODS:
We reviewed the medical records of 6 patients with ARC syndrome among 90 patients with neonatal cholestasis from 2000 to 2005 and assessed the relative incidence rate ratio, clinical symptoms, laboratory findings, and pathological findings. DNA samples from 5 patients, 4 parents, and 2 fetuses were analyzed for VPS33B mutations.
RESULTS:
The relative incidence rate ratio was 1/7 that of biliary atresia (95% CI 0.33-0.06). All 6 patients presented with ichthyosis and recurrent infection, and failed to thrive with the 3 main symptoms. All of the patients died within the age of 12 months. They had various severities of cholestasis, metabolic acidosis, nephrogenic diabetes insipidus, chronic diarrhea, platelet abnormalities, and central nervous system anomalies. We identified 1 novel c.403+2T>A splice-site mutation, 2 frame-shift mutations (c.1509_1510insG, c.790_791del), 1 nonsense mutation (c.661C>A), and 1 known nonsense mutation (c.1518C>T) in the VPS33B gene. Prenatal diagnosis was performed in 2 different families.
CONCLUSIONS:
This study indicates that the incidence of ARC syndrome is not as rare as has been thought. We found 4 novel and 1 known mutations in ARC syndrome patients and performed prenatal diagnosis in 2 families, which will facilitate genetic diagnosis and counseling for affected families.
AuthorsJoo Young Jang, Kyung Mo Kim, Gu-Hwan Kim, Eunsil Yu, Jin-Joo Lee, Young Seo Park, Han-Wook Yoo
JournalJournal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 48 Issue 3 Pg. 348-54 (Mar 2009) ISSN: 1536-4801 [Electronic] United States
PMID19274792 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • VPS33B protein, human
  • Vesicular Transport Proteins
Topics
  • Abnormalities, Multiple (genetics)
  • Arthrogryposis (genetics)
  • Biliary Atresia (genetics)
  • Cholestasis (genetics)
  • Failure to Thrive (genetics)
  • Fatal Outcome
  • Female
  • Humans
  • Ichthyosis (epidemiology, genetics)
  • Incidence
  • Infant
  • Infections (complications, epidemiology, genetics)
  • Kidney Diseases (genetics)
  • Korea (epidemiology)
  • Male
  • Mutation (genetics)
  • Syndrome
  • Vesicular Transport Proteins (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: