Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a multisystem disorder characterised by abnormalities of the renal, hepatic, musculoskeletal and central nervous system. The clinical features of ARC syndrome include arthrogryposis, renal tubular acidosis, and neonatal cholestatic jaundice. Additional symptoms may present, such as ichthyosis, platelet anomalies, agenesis of the corpus callosum, deafness, recurrent infection, and internal bleeding owing to coagulation dysfunction.
Homozygous or compound heterozygous mutations in the VPS33B gene is known to cause ARC1.
Mikati et al. (1984) reported two Lebanese siblings (male) with ARC syndrome. Several characteristic features of the syndrome were observed, such as proximal renal tubular insufficiency, cholestatic jaundice, and multiple congenital anomalies. The patients had micrognathia, low set ears, high arched palate, barrel shaped chest, bilateral simian creases, club feet, congenital hip dislocation, hypotonia, conjugated hyperbilirubinemia and severe failure to thrive. The infants were reported to have died at the ages of 2 and 4 months. In a letter written by Mikati in 2007, he emphasized that the two Lebanese patients had severe right ventricular hypertrophy identified through electrocardiography, in addition to immune deficiency and ichthyosis.
Abu-Sa’da et al. (2005) reported two unrelated Saudi infants with ARC syndrome. The first patient was an infant boy born to first degree cousins, who shortly after birth, suffered from jaundice, diarrhea and failure to thrive. He had multiple blood disorders, febrile illness, dehydration and metabolic acidosis, until the age of seven months when he died. The second patient was a female infant, also born to first cousin parents. At birth, she had fracture of her right femur, developmental dysplasia of hips and severely ichthyotic skin. Other conditions included metabolic acidosis and Fanconi syndrome, jaundice, and recurrent sepsis. She was hospitalized at the age of three months, where she was observed to be febrile, hypotensive, and severely dehydrated. She died on the second day with sepsis and irreversible shock.