Arthrogryposis, Renal Dysfunction and Cholestasis (ARC) Syndrome is a rare multisystemic disorder that presents at birth or infancy. The mutation protein is involved in the regulation of vesicle-to-target SNARE complex formation and membrane fusion.

Gene affected: VPS33B (vacuolar protein sorting 33 homolog B)


Chromosome: 15q26.1


Inheritance: autosomal recessive


Clinical features:

(1) arthrogryposis multiplex congenita (congenital joint contractures in >= 2 areas of the body)

(2) renal tubular dysfunction (Fanconi-type renal tubular acidosis, nephrogenic diabetes insipidus)

(3) neonatal conjugated hyperbilirubinemia with bile duct hypoplasia


Variable findings:

(1) ichthyosis

(2) central nervous system malformation

(3) deafness

(4) platelet dysfunction (abnormal appearance with marked reduction in alpha-granules)

(5) hypotonia

(6) failure to thrive

(7) FUO


Laboratory findings (in addition to above):

(1) low or normal serum GGT

(2) variable aminoaciduria

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