A Novel, Likely Pathogenic MAX Germline Variant in a Patient With Unilateral Pheochromocytoma

Abstract

Objective Inherited MAX gene pathogenic variants (PVs) increase risk for pheochromocytomas (PCCs) and/or paragangliomas (PGLs) in adults and children. There is little clinical experience with such mutations. This report highlights an important approach. Methods Clinical assessment, including blood chemistry, imaging studies, and genetic testing were performed. Results A 38-year-old Hispanic woman was diagnosed with PCC in 2015, treated with adrenalectomy and referred to endocrinology clinic. Notably, she presented to her primary care physician three years earlier complaining of left flank pain, intermittent diaphoresis and holocranial severe headache. We confirmed severe hypertension (180/100 mmHg) over multiple antihypertensive regimens. Biochemical and radiological studies work-up revealed high plasma metanephrine of 255 pg/mL (normal range < 65), and plasma normetanephrine of 240 pg/mL (normal range < 196). A non-contrast computed tomography scan of the abdomen revealed a 4.2 x 4.3 x 4.9 cm, round-shaped and heterogenous contrast enhancement of the left adrenal gland, and a 2-mm nonobstructive left kidney stone. A presumptive diagnosis of secondary hypertension was made. After pharmacological therapy, laparoscopic left adrenalectomy was performed and confirmed the diagnosis of pheochromocytoma. Based on both her age, family history and a high suspicion for genetic etiology, genetic testing was performed which revealed the presence of a novel likely pathogenic variant involving a splice consensus sequence in the MAX gene, designated c.64-2A> G). Conclusion The phenotype of MAX PV-related disease and paraganglioma are highlighted. The novel c.64-2A> G mutation is reported here and should be considered on the diagnostic work-up of similar cases.

Bilateral Pheochromocytoma with Germline MAX Variant without Family History

“…Among 499 studies, 213 articles reported variants related to PPGLs and 16 papers reported MAX variants. We summarized the characteristics of the cases with PPGLs in MAX variants [ 5 , 15 , 16 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ] ( Supplementary Table S1 ). Combining data from the 16 reports in MAX variants revealed that 42/71 cases (59.2%) had bilateral PCCs, 9/59 cases (8.5%) had PGLs, and 31/70 cases (44.3%) had an apparent family history of PPGLs.…”