From the Department of Internal Medicine (J.R., M.D.), the Division of Gastroenterology and Hepatology (D.H.-D., T.S.), the Department of Medical Oncology, Sidney Kimmel Cancer Center (A.B.M., D.S.L.), the Department of Surgery (H.L., W.M., A.P.S.), the Division of Endocrinology, Diabetes, and Metabolic Diseases (J.M.), and the Department of Pathology and Genomics (M.A.), Thomas Jefferson University, the Department of Medical Oncology, Fox Chase Cancer Center (N.V.), and the Division of Human Genetics, Children's Hospital of Philadelphia (R.G.) - all in Philadelphia; the Division of Clinical Cancer Genetics, Section of Medical Oncology, Department of Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT (V.N.G.); and the Division of Endocrinology, Diabetes, and Metabolism, David Geffen School of Medicine at UCLA, Los Angeles (R.Y.).
Published: November 2023
AI Article Synopsis
Article Abstract
Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.
Division of Endocrinology, Diabetes, and Metabolism, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, United States.
Radiologists play a key role in establishing an early and accurate diagnosis, especially for rare diseases. Mahvash disease (OMIM 619290) is an autosomal recessive hereditary disease caused by inactivating mutations of the glucagon receptor and its main clinical consequences are pancreatic neuroendocrine tumors and in some cases, porto-sinusoidal vascular disease and portal hypertension. Untreated Mahvash disease can be lethal.
Mahvash disease, a rare autosomal recessive metabolic disorder characterized by biallelic loss-of-function mutations in the glucagon receptor gene (), induces significant pancreatic hyperglucagonemia, resulting in α-cell hyperplasia and occasional hypoglycemia. Utilizing CRISPR-Cas9 technology, we engineered a mouse model, designated as , harboring a homozygous V369M substitution in the glucagon receptor (GCGR). Although wild-type (WT) and mice exhibited no discernible difference in appearance or weight, adult mice, approximately 12 months of age, displayed a notable decrease in fasting blood glucose levels and elevated the levels of cholesterol and low-density lipoprotein-cholesterol.
Medullary thyroid carcinoma (MTC) can often have an indolent course despite distant metastatic disease. Additionally, given that metastatic MTC is incurable and systemic therapies have non-negligeable toxicities, localized treatments are often favored in presence of oligo-progressive disease. Transarterial radioembolization (TARE) with yttrium-90 (Y90) has emerged as a safe and efficacious treatment for nonresectable primary and metastatic liver tumors, yet data supporting its use in metastatic MTC are limited.
Pancreatic neuroendocrine neoplasms (panNENs) have been historically regarded as rare, but their incidence has raised more than 6-fold over the last 3 decades, mostly owing to improvement in the detection of small asymptomatic tumours with imaging. Early detection and proper classification and staging are essential for the prognosis and management of panNENs. Histological evaluation is mandatory in all patients for the diagnosis of panNEN.
