Pitfall in the Diagnosis of Fructose-1,6-Bisphosphatase Deficiency: Difficulty in Detecting Glycerol-3-Phosphate with Solvent Extraction in Urinary GC/MS Analysis

Fructose-1,6-bisphosphatase deficiency as a cause of recurrent hypoglycemia and metabolic acidosis: Clinical and molecular findings in Malaysian patients

“…phosphate detection in patients with FBPase deficiency, including urine samples collected during asymptomatic period. 4,12 The use of electrospray ionization tandem mass spectrometry in negative-ion mode can also improve the detection of glycerol phosphate in urine samples. 13 Pseudo-hypertriglyceridemia is another useful biomarker in the diagnosis of FBPase deficiency.…”

“…1,2 FBPase deficiency may be suspected by detecting elevated urinary excretion of glycerol or glycerol-3-phosphate. 3,4 Direct enzymatic assay of hepatic FBPase activity remains the most specific diagnostic test for FBPase deficiency, but this is only performed by a handful of reference laboratories. Molecular study is increasingly performed to confirm the diagnosis.…”

“…It is located at chromosome bands 9q22.2-q22.3. 4 Currently, about 35 mutations in the FBP1 gene have been reported and the majority are private mutations. The notable exceptions are c.959dupG and c.-24-26_170 þ 5192del, which are recurring among Caucasians and Japanese, and patients from Turkey and Armenia, respectively.…”

Clinical and molecular characterization of Indian patients with fructose‐1, 6‐bisphosphatase deficiency: Identification of a frequent variant (E281K)

“…However, a major challenge in these children is a timely and accurate diagnosis. The presence of glycerol and glycerol 3‐phosphate in urine GC‐MS is able to confirm the diagnosis in FBP1‐deficient patients, but these findings are dependent on several factors, including time of sampling during acute illness, and are not always present (Kato et al., ). Molecular studies are very helpful in accurately diagnosing this condition.…”

A Japanese boy with fructose-1,6-bisphosphatase deficiency who had a novel <i>FBP1</i> mutation (p.Phe90Val)

“…(2015) reported a case of FBPase deficiency in which the excretion level of glycerol-3-phosphate in the urine during a fasting episode was at a normal level based on GC/MS analysis after solvent extraction ( 6 ). However, excretion of glycerol-3-phosphate in the same sample was found to be increased when analyzed using GC/MS with the urease pretreatment non-extraction method ( 6 ). In our case, the normal value of glycerol-3-phosphate excretion in the urine was a false-negative, although the urine sample was analyzed using GC/MS with the urease pretreatment non-extraction method.…”