Abstract
Rare heterozygous loss-of-function mutations of the MAX gene are associated with autosomal dominant hereditary pheochromocytoma-paraganglioma syndrome. In addition, evidence suggests that pathogenic MAX mutation may predispose to the development of other tumors, including endocrine and nonendocrine tumors, although the number of reported cases is small. We report a 67-year-old man with bilateral pheochromocytoma, primary hyperparathyroidism, prostate cancer, neurofibroma, and abdominal wall lipoma who tested positive for a heterozygous pathogenic germline MAX mutation. The patient has a history of bilateral norepinephrine-producing pheochromocytomas, for which he underwent left and right adrenalectomy in his 20s and 30s, respectively. His long-standing primary hyperparathyroidism was first documented when he was 40 years old and complicated by recurrent bilateral calcium oxalate nephrolithiasis and early-onset osteoporosis. Genetic testing revealed a heterozygous pathogenic deletional frameshift mutation of the exon 4 of the MAX gene (c.183_195del; p.Gln62Lysfs*104). This report, together with 3 previously reported cases, suggests that germline MAX mutation may contribute to the development of primary hyperparathyroidism and may be considered in suspected genetic forms of this disease.