Mahvash disease: A novel case of apparent monoallelic disease and a novel cause of hypoglycaemia

Abstract

Glucagon cell hyperplasia and neoplasia (GCHN), also known as Mahvash disease (MVAH), is a rare pancreatic neuroendocrine disorder. In most cases, the disorder is autosomal recessive and caused by inactivating mutations in the glucagon receptor (GCGR), leading to pancreatic α-cell hyperplasia and hyperglucagonemia, with sporadic association with hypoglycaemia. We present an adult female patient presenting with recurrent hypoglycaemia: she had an enlarged pancreas and very high levels of glucagon. Severe hypoglycaemia is not generally seen in most cases of Mahvash syndrome; this could suggest the possibility of an occult insulinoma. Genetic testing showed an essential splice variant in GCGR that predicts loss of protein production. It is most likely a single pathogenic variant in the GCGR gene, although the literature reports only a recessive phenotype. We cannot entirely exclude an autosomal recessive condition in terms of mutations in promoter or relevant intronic regions