Mahvash Disease: An Autosomal Recessive Hereditary Pancreatic Neuroendocrine Tumor Syndrome

Abstract

Mahvash disease is a rare autosomal recessive hereditary pancreatic neuroendocrine tumor syndrome characterized by inactivating mutations in the glucagon receptor, hyperglucagonemia without symptoms of the glucagonoma syndrome, pancreatic α-cell hyperplasia and pancreatic neuroendocrine tumors. In Mahvash disease, the lack of negative feedback from glucagon receptor signaling results in compensatory hyperplasia of pancreatic α-cells and secondary tumorigenesis. Over ten clinical cases consistent with Mahvash disease have been reported thus far, most of which have confirmed biallelic mutations in the glucagon receptor. Mahvash disease provides insight into glucagon signaling pathway regulation and pathogenesis of pancreatic neuroendocrine tumors.