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[39] further linked APOE4-associated vascular dysfunction to overactivation of mTOR

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Although saccharopinuria is generally considered benign, there are reports indicating impaired function of the urea cycle, hyperammonemia, hypercitrullinemia, intellectual impairment, and neurological problems [39]

Ammonia is known to alter mitochondrial permeability, leading to mitochondrial swelling and dysfunction.6 In addition, hyperactivation of NMDA receptors activates neurotoxic pathways conducting to axonal degeneration and cellular death.5 Another hypothesis of brain impairment is the activation of the phosphatase calcineurin, which increases the ATP consumption by 80% through the Na/K ATPase dephosphorylation