Signs and symptoms
Most patients with Mahvash disease are diagnosed in adulthood. Patients with Mahvash disease usually present with vague abdominal discomfort. Imaging with CT or MRI identifies a very large pancreas with one or more tumors. Biochemical testing shows marked hyperglucagonemia (hundreds-fold elevated). If the tumors are resected, they are found to be neuroendocrine tumors that usually express glucagon. In the tumor margin, pancreatic alpha cell hyperplasia is pervasive, numerous largePathogenesis
Mahvash disease is a form of reactive pancreatic alpha cell hyperplasia. The loss of normal glucagon signaling (particularly in the liver) due to inactive glucagon receptor results in enzymatic changes in the liver so that the liver releases abnormally large quantities of amino acids into the circulation. High concentration of amino acids in the circulation ( hyperaminoacidemia) stimulates the pancreatic alpha cells (the cells that normally produce glucagon) to proliferate and to produce and release much more glucagon. The enormous proliferative activity of the pancreatic alpha cells predisposes them to tumor formation. All patients with Mahvash disease have hyperaminoacidemia, hyperglucagonemia (high concentration of glucagon in the circulation), and pancreatic alpha cell hyperplasia, and developDiagnosis
A large pancreas with marked hyperglucagonemia in an adult makes the diagnosis of Mahvash disease very likely. The existence of pancreatic tumors makes the diagnosis even more likely. Histologically, pancreatic alpha cell hyperplasia and microadenomas suggest the diagnosis of Mahvash disease. The final diagnosis of Mahvash disease requires genetic test of the glucagon receptor gene.Treatment
The treatment of Mahvash disease currently focuses on managing the pancreatic neuroendocrine tumors. Small tumors can be monitored but large ones need to be resected. As patients with Mahvash disease have life-long risk of developing pancreatic neuroendocrine tumors, they need to undergo periodic biochemical testing and imaging.References
{{Medical resources , DiseasesDB = , ICD10 = E16.3 , ICD9 = , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = 118899 , MeshID = , Orphanet = 438274 , GARD = 10460 Autosomal recessive disorders Rare syndromes