Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria

This study describes a patient with severe germline VHL deficiency due to a novel synonymous mutation (c.222C→A, p.V74V), leading to marked erythrocytosis and systemic metabolic alterations. The condition differs from Chuvash polycythemia, presenting with early onset growth retardation, persistent hypoglycemia, and limited exercise capacity. The research highlights significant mitochondrial dysfunction, including impaired respiratory activity and unusual intermitochondrial connecting ducts, alongside metabolic shifts favoring glycolysis over oxidative phosphorylation. The findings underscore the critical role of the VHL-HIF axis in human growth, metabolism, and mitochondrial function.

This study describes a patient with severe germline VHL deficiency due to a novel synonymous mutation (c.222C→A, p.V74V), leading to marked erythrocytosis and systemic metabolic alterations. The condition differs from Chuvash polycythemia, presenting with early onset growth retardation, persistent hypoglycemia, and limited exercise capacity. The research highlights significant mitochondrial dysfunction, including impaired respiratory activity and unusual intermitochondrial connecting ducts, alongside metabolic shifts favoring glycolysis over oxidative phosphorylation. The findings underscore the critical role of the VHL-HIF axis in human growth, metabolism, and mitochondrial function.