Tohoku J. Exp. Med., 2015 November, 237(3)

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

SAYAKA KATO,¹ YOKO NAKAJIMA,² RISA AWAYA,³ IKUE HATA,⁴ YOSUKE SHIGEMATSU,⁵ SHINJI SAITOH¹ and TETSUYA ITO²

¹Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
²Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
³Department of Pediatrics, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Aichi, Japan
⁴Department of Pediatrics, University of Fukui Faculty of Medical Sciences, Fukui, Fukui, Japan
⁵Department of Health Science, University of Fukui Faculty of Medical Sciences, Fukui, Fukui, Japan

Fructose-1,6-bisphosphatase (FBPase), an enzyme involved in gluconeogenesis, catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate. FBPase deficiency is an autosomal recessive inherited disorder, characterized by episodic attacks of hypoglycemia, ketosis, and lactic acidosis during fasting. In general, urinary organic acid analysis using gas chromatography-mass spectrometry (GC/MS) is very useful for the diagnosis of FBPase deficiency, because the appearance of glycerol or glycerol-3-phosphate in the urine is characteristic of this disease. Here, we report a case of FBPase deficiency in a girl with a history of several severe lactic acidosis events, both as a neonate and after the age of 12 months. The patient was identified as a compound heterozygote with two mutations in the FBPase 1 gene: c.841G>A (p.Glu281Lys) and c.960_961insG (p.Ser321fs). The c.841G>A is a newly identified pathogenic mutation. An abnormal level of glycerol-3-phosphate was not detected in the conventional urinary organic acid analysis using GC/MS after solvent extraction. This method, which is a widely used diagnostic standard, could not detect increased levels of glycerol or glycerol-3-phosphate in the patient's urine, which was sampled during the episode. However, glycerol and glycerol-3-phosphate were detected in the same sample, when it was analyzed using GC/MS with the urease pretreatment non-extraction method. Patients with FBPase deficiency have good glycemic control after correct treatment. Therefore, accurate and early diagnosis is essential for a good prognosis. Accordingly, when a patient presents with hypoglycemia and lactic acidosis, it is important to select the appropriate method of urinalysis for organic acids by GC/MS.

keywords —— fructose-1,6-bisphosphatase deficiency; GC/MS analysis; gluconeogenesis; hypoglycemia; lactic acidosis

© 2015 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2015, 237, 235-239

Correspondence: Tetsuya Ito, Department of Pediatrics, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.

e-mail: itotetsu@fujita-hu.ac.jp