(acronym for Arthrogryposis, Renal dysfunction, and Cholestasis)

Very rare, this syndrome seems to be more frequent in Saudi Arabia and Pakistan. Combination of arthrogryposis, tubular acidosis and cholestasis, sometimes associated with a thrombopathy similar to the gray platelets syndrome (see that term).

A distinction is made between :

* type 1 or ARCS1, [MIM 208 085], the most common: autosomal recessive transmission of a mutation of the VPS33B gene (15q26.1) (75 %), coding for the Vps33p protein.  This protein is involved in complex cellular functions involved in intracellular vesicle trafficking. 
Death usually occurs during the first year of life.

* type 2 or ARCS2 [MIM 613 404] autosomal recessive transmission of a mutation of the VIPAS39 (14q24) or VIPAR gene, coding for a protein that forms a functional complex with Vps33p. The clinical picture is less severe than in type 1, and survival is better.

Clinical features

-         arthrogryposis: clubfoot, hip and knee contractures,

-         tubular acidosis with proteinuria, hyperchloremic acidosis (Fanconi syndrome)

-         intrahepatic cholestasis with low γGT levels, sometimes severe pruritus

-         poor growth, frequent infections

-         ichthyosis and hyperkeratosis,   

-         platelet abnormalities: absence of alpha granules and aggregation disorders

-         large hands

-         low-set ears, arched palate, receding forehead

-         hypothyroidism

-         hearing disorders

-         moderate intellectual deficit

-         agenesis of corpus callosum.

Anesthetic implications: 

Check liver and kidney function. Risk of bleeding: check platelet morphology and function.

References : 

-        Hayes JA, Khar WHA, Lo B, McPherson BA.
Liver biopsy complicated by hemorrhage in a patient with ARC syndrome. Pediatr Anesth 2004; 14: 960-3.- Jang JY, Kim KM, Kim GH, -  - Yu E, Lee JJ, Park YS, Yoo HW. Clinical characteristics and VPS33B mutations in patients with ARC syndrome.
J Pediatr Gastroenterol Nutr 2009; 48:348-54.

-        Dehghani SM, Bahador A, Nikeghbalian S, Salahi H, Geramizadeh B, Malekpour A, et al.
Liver transplant in a case of arthrogryposis-renal tubular dysfunction-cholestasis syndrome with severe intractable pruritus.
Exp Clin Transplant 2013;11:290–2.

-        Kafol J, Gnidovec Strazisar B, Drole Torkar A, Homan M, Bertok S, Mlinaric M, Sikonja J, Kovač J.
VIPAS39 related arthrogryposis‑renal dysfunction‑cholestasis syndrome-case reportand systematic review.
Orphanet Journal of Rare Diseases 2024; 19:496

Updated: January 2025