(Multiple paragangliomas with erythrocytosis)

Very rare. Mosaic mutation with gain in function of the EPAS1 gene (or HIF2A for hypoxia-inducible factor 2-alpha)(2p21) leading to a secondary increased expression of other genes such as EPO (erythropoietin), GLUT1 (glucose transporter member 1), VEGFA (vascular endothelial growth factor á) and END1 (endosperm). 

Association of:

• polycythemia which is usually the first sign, discovered in early childhood
• multiple paragangliomas (sometimes pheochromocytomas), which usually appear in adolescence.
• digestive somatostatinoma (usually duodenal).

The arteries of the fundus may be tortuous with a choroidal thickening.

Belzutifan is an EPASI inhibitor that causes regression of the tumor and the polycythemia.

Anesthetic implications:

risk of catecholamine secretion by the paraganglioma (see pheochromocytoma); increased thromboembolic risk in case of polycythemia

References :

-        Vicha A, Mercado-Asis LB.
Pacak-Zhuang syndrome: a new kid on the block.
Endocr Pract. 2014; 20 : DOI: 10.4158/endp.20.11.g37v757188j41v24

-        Abdallah A, Pappo A, Reiss U, Shulkin BL, Zhuang Z, Pacak K, Bahrami A.
Clinical manifestations of Pacak-Zhuang syndrome in a male pediatric patient.
Pediatr Blood Cancer 2020 April ; 67(4): e28096. doi:10.1002/pbc.28096

Updated: April 2022