GLUL and hypophosphatasia: Without treatment, HPP mice died by 20 days of age.(22,35) The major cause of death in the untreated HPP mice was apnea, most likely resulting from their severe epileptic convulsions.(21) Pyridoxine-responsive seizures in HPP patients and HPP model mice are thought to be caused by reduced levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain.(21,35) PLP is an essential cofactor of glutamate decarboxylase, which is responsible for the synthesis of GABA.(41) Diminished hydrolysis of extracellular PLP in HPP causes decreased intracellular pyridoxal levels in cells.