Rapid, simplified and sensitive method for screening fructose-1,6-diphosphatase deficiency by analyzing urinary metabolites in urease/direct preparations and gas chromatography–mass spectrometry in the selected-ion monitoring mode

Children with fructose-1,6-diphosphatase (FDPase) deficiency often experience life threatening episodes such as ketotic hypoglycemia. We report here a rapid, simplified and sensitive method to analyze glycerol-3-phosphate (G3P) and glycerol in urine, that can be used to detect FDPase deficiency. We used the urease/direct preparation and gas chromatography–mass spectrometry in the selected-ion monitoring mode, enabling detection of G3P and glycerol level in normal controls. Using this approach, FDPase deficiency can be more easily diagnosed and differentiated from glycerol kinase deficiency or glycerol infusion patients. To date, diagnosis has been essentially based on the assay of enzymes in the liver. The proposed non-invasive method provides a clinically significant diagnostic tool that may help prevent episodic attacks.