Platelet Functional And Morphological Abnormalities In A Case Of Arthrogrysosis, Renal Dysfunction And Cholestasis (Arc) Syndrome With A Novel Genetic Profile

ARC syndrome is a severe autosomal recessive multisystem disorder characterized by arthrogryposis, neonatal cholestatic jaundice, renal tubular acidosis, failure to thrive, dysmorphic features, congenital heart disease, cerebral malformation, hypotonia, recurrent febrile illness and a bleeding disorder. It is associated with consanguinity and most patients do not survive beyond the first year of life. ARC syndrome is linked to loss of function in either VPS33B or VIPAS39, respectively encoding VPS33B and VPS16B, which we have shown to be interaction partners within a multiprotein complex involved in intracellular vesicular trafficking (Urban et al, Blood. 2012 Dec 13;120(25):5032-40). Earlier we determined that bleeding problems in ARC syndrome patients (where platelet aggregation abnormalities have been observed) arise from abnormal function of normally abundant platelets lacking α-granules (Lo et al, Blood. 2005;106(13):4159-66). Detailed studies of ARC syndrome platelets have been hampered by limited availability.