Arthrogryposis-renal dysfunction-cholestasis syndrome (ARC syndrome)

ARC syndrome is an autosomal recessive disease characterised by immobility of the limbs and fixation of joints with muscle wasting (neurogenic arthrogryposis multiplex congenita), renal tubular dysfunction and neonatal cholestasis.8
ARC syndrome is a life-threatening disorder. Although the prevalence is unknown, fewer than 100 patients have been reported in the literature.3,8

The phenotype is variable and may include:3

  • Renal tubular dysfunction of variable severity
  • Hepatic anomalies, including cholestasis, intrahepatic biliary duct hypoplasia and lipofuscin deposition
  • Severe failure to thrive, diarrhoea, recurrent febrile illness
  • Cerebral malformations
  • Sensorineural deafness
  • Platelet dysfunction
  • Facial dysmorphism (low set ears, lax skin, a high arched palate, beaked nose and small anterior fontanelle)
Diagnosis

The clinical diagnosis consists of identifying:

  • Arthrogryposis
  • Renal tubular acidosis
  • Neonatal cholestatic jaundice with low GGT activity
Diagnosis is confirmed by sequence analysis of VPS33B and VIPAR.8
Back to diagnostic algorithm

3. INSERM. Orphanet. European Union: The portal for rare diseases and orphan drugs. 2021 (accessed 09/2021 at https://www.orpha.net/consor/cgi-bin/Disease.php?lng=EN.)

8. Zhou Y, Zhang J. Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: from molecular genetics to clinical features. Ital J Pediatr 2014;40:77.