#6286 NEPHROCALCINOSIS IN 3 GENERATIONS OF FEMALE PATIENTS DUE TO A PATHOGENIC MEN1 MUTATION

Abstract

Abstract Background and Aims Multiple Endocrince Neoplasia type 1 (MEN1) syndrome, has an autosomal dominant transmission pattern, characterized by hyperparathyroidism, benign or malignant tumors in pancreas islets, pituitary tumors, thymic carcinomas, adrenal cortex adenomas and angio-fibromas of the skin. We are describing 2 cases of MEN1 with first and cardinal manifestations within the kidney. Method Medical records review, whole exome sequencing (WES), bioinformatics analysis by Ingenuity Pathway Analysis, QIAGEN Results Patient 1. A 28 year old female presented with horseshoe kidney, multiple pyelonephritis episodes, primary hyperparathyroidism, hypercalcemia, magnesiuria, reduced bone mass, and nephrocalcinosis. Her mother and grandmother suffered from hyperparathyroidism. WES analysis demonstrated a 12-base deletion between intron 9 and exon 10 in MEN1 gene (c.1351-3_1359delCAGGTGCGGCAG) with an apparent pathogenicity [1]. An accompanying alteration of CLDN16 gene (c.324+13C>G, rs369250510) was also detected. Till now this alteration is considered benign. Patient 2. A 48 year old female, with primary hyperparathyroidism in the last 15 years (the mother of Patient 1), with nephrocalcinosis since 1997 (calcium oxalate stones), preserved renal function, hypercalcemia, magnesiuria, reduced bone mass, hypertelorism with concurrent diplopia. In 2013, parathyroeidectomy resulted in stabilization of nephrocalcinosis. WES revealed the same pathogenic deletion as in her daughter. A research for epigastric pain revealed a cystic pancreatic mass, with accompanying increase in serum gastrin and chromogranin. A pituitary adenoma is manifested with a marginally increased serum prolactin. Her mother suffers from primary hyperparathyroidism with nephrocalcinosis. Conclusion In familial nephrocalcinosis/lithiasis/hyperparathyroidism genetic counselling and screening defines individualized treatment and may prevent extra renal disease manifestations.