Investigators at Bambino Gesu Children’s Hospital, Rome, and other centers in Italy, Canada and France report an 8-year-old female Sephardic-Jewish patient with MEDNIK syndrome associated with a new AP1S1 homozygous mutation. She showed severe perturbations of copper metabolism with hypocupremia, hypoceruloplasminemia and liver copper accumulation with intrahepatic cholestasis. Treatment with zinc acetate resulted in improved clinical symptoms and liver copper metabolism. Reevaluation of 5 original French-Canadian patients with MEDNIK syndrome and AP1S1 mutations confirmed copper metabolism perturbation and hepatopathy in all patients. In the pathogenesis of MEDNIK syndrome, AP1S1 regulates intracellular copper machinery mediated by copper-pump proteins. This multisystem treatable disease combines clinical and biochemical signs of both Menkes and Wilson’s diseases. [1]
COMMENT. MEDNIK syndrome is an acronym for mental retardation, deafness, neuropathy, ichthyosis, and keratodermia, and is caused by AP1S1 gene mutations. This rare autosomal recessive neurocutaneous syndrome, first reported in French-Canadian families [2], is now known to be caused by a perturbation of copper metabolism, and is treatable with zinc acetate.