The following summary is from Orphanet
, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 2697
A rare, multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with low serum gamma-glutamyl transferase activity.
The prevalence is unknown but less than 100 patients have been reported in the literature so far.
The phenotype is variable, even within the same family and cases may go undiagnosed as not all the patients present with the three cardinal features. Renal tubular dysfunction ranges from isolated renal tubular acidosis to complete Fanconi syndrome (polyuria, aminoaciduria, glycosuria, phosphaturia and bicarbonate wasting). Hepatic anomalies include variable combinations of cholestasis, intrahepatic biliary duct hypoplasia and lipofuscin deposition. Additional features include severe failure to thrive, platelet dysfunction (which may be responsible for severe bleeding), facial dysmorphism (low set ears, lax skin, a high arched palate, beaked nose and small anterior fontanelle), diarrhea, recurrent febrile illness, cerebral malformations and sensorineural deafness.
Mutations in the VPS33B gene (15q26.1), involved in intracellular protein trafficking and membrane fusion, have been found in 75% of ARC families, as well as mutations in the VIPAR gene (C14ORF133), encoding a protein that complexes with VPS33B.
The differential diagnosis should include progressive familial intrahepatic cholestasis disorders, other forms of arthrogryposis multiplex congenita and congenital ichthyosiform dermatoses (see these terms).
The syndrome is generally considered to be transmitted as an autosomal recessive trait.
Management and treatment
There is no specific treatment for the disease.
Most patients die within the first year of life despite supportive care for metabolic acidosis and cholestasis and those surviving longer show cirrhosis and severe developmental delay.
Last updated: 6/1/2010