Arthrogryposis–renal dysfunction–cholestasis (ARC) syndrome: from molecular genetics to clinical features

Abstract

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare but fatal autosomal recessive multisystem disorder caused by mutations in the VPS33B or VIPAR gene. The classical presentation of ARC includes congenital joint contractures, renal tubular dysfunction, and cholestasis. Additional features include ichthyosis, central nervous system malformation, platelet anomalies, and severe failure to thrive. Diagnosis of ARC syndrome relies on clinical features, organ biopsy, and mutational analysis. However, no specific treatment currently exists for this syndrome.ConclusionThis is an overview of the latest knowledge regarding the genetic features and clinical manifestations of ARC syndrome. Greater awareness and understanding of this syndrome should allow more timely intervention with potential for improving long-term outcome.

Arthrogryposis-renal tubular dysfunction-cholestasis syndrome: a cause of neonatal cholestasis. Case report

“…Therefore,only supportive care including high fluid and caloric administration such as total parenteral nutrition or medium chain triglyceriderich formulas, monthly vitamin A-D-E-K and ursodeoxyhcolic acid can be given. 2 Our patient died at 37 days of age because of sepsis.…”

“…Osteopenia and pathological fractures can be observed in this syndrome owing to reduced reabsorption of phosphate ions via renal tubules and secondary to hyperparathyroidism. 2 Our patient was hypotonic and had radial deviation of the wrist, flexion contracture of the knee joints and bilateral calcaneovalgus. Ultrasonography revealed dislocation of both hip joints.…”

“…Renal tubular dysfunction may present in the first few days of life or later around the age of two to three months. 2,8,9 Most of the patients also present symptoms of nephrogenic diabetes insipidus.Renal ultrasonography may reveal nephrocalcinosis or a small dysplastic kidney. 5,9 Our case had renal tubulopathy and nephrogenic diabetes insipidus.…”

“…1 The prognosis of the syndrome is poor and most patients die by the age of 7 months because of recurrent infections, severe dehydratation, metabolic acidosis or internal hemorrhaging. 2,3 We report this case since it was rapidly fatal.…”

ARC Syndrome and Platelet’s Abnormalities about Two Cases

“…It's an autosomal recessive disease due to a mutation in the VP33B gene on chromosome 15q26.1 [2]. The cardinal clinical features of the syndrome include cholestasis with normal serum gamma-glutamyltranspeptidase (g-GT) activity, arthrogryposis, and renal disorders (renal failure, renal tubular dysfunction) [1][2][3]. Bleeding problems have also been observed in this syndrome secondary to abnormal platelet's morphology and function.…”