Six year male child presented with hypoglycaemia and metabolic acidosis having history of recurrent episodes of hypoglycemic convulsions and more than ten hospital admissions for similar complaints. First episode occurred on day second of life with refusal to feed, respiratory distress, hypoglycemia and metabolic acidosis. Based on the examination and investigations results at that time, Glycogen Storage Disorder (GSD) was suspected. Treatment and management for the same was started. Various investigations done during remission period were normal except elevated blood lactate. At 6 years index case had episode of hypoketotic hypoglycaemia with metabolic acidosis. Considering this presentation GSD was ruled out. Fatty acid oxidation disorder was suspected and metabolic work up done which was normal. During current episode advanced metabolic investigations–urinary gas chromatography–mass spectrometry analysis revealed increased excretion of lactate, glycerol-3phsphate and glycerol suggesting Fructose 1, 6-diphosphatase deficiency (FDPD). Management for FDPD was started immediately and was monitored closely. In last 3 years the child has not a single episode and is attending normal school. Therefore, it is important to subject the child to advance and comprehensive metabolic investigation such as urinary GC-MS profiling as soon as possible in such cases. The timing for collection of sample is key in many such disorders as the metabolic abnormality might not show up during remission and hence the blood & urine sample collection during the episode is of utmost importance to arrive at a diagnosis. An accurate diagnosis through timely collection of sample, advanced metabolomics techniques and targeted management regime can go a longway in determining the outcome and prognosis in such cases.

Keywords: Fructose-1, 6-diphosphatase Deficiency, hypoglycaemia, hepatospleenomegaly, metabolic acidosis

1.      Emery JL, Howat AJ, Variend S, Vawter GW (1996): Investigation of inborn errors of metabolism inunexpected infant deaths. Lancet8601:29-31

2.      Matsumoto I and Kuhara T (1996): A new chemical diagnostic method for inborn errors of metabolism by mass spectrometry-rapid, practical and simultaneous urinary metabolites analysis.  Mass Spectrometry Reviews.15:43-57

3.      Baker L, and Winegrad Al (1970): Fasting hypoglycemia and metabolic acidosis associated with deficiency of hepaticfructose-1, 6-bisphosphatase activity. Lancet II. 13-16

4.      Huidekoper HH, Visser G, Ackermans MT, Sauerwein HP, Wijburg FA (2010): A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1 and fructose-1, 6-bisphosphatase deficiency. J. Inherit Metab Dis.33:25-31

5.      Browning JD, Baxter J RN, Satapathi S and Burgess SC. (2012): The effect of short –term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men. J Lipid Res.Mar; 53(3),557-586

6.      Takagi D, Ben-Ari J, Nemet D, Zeharia A, Eliakim A. 2012): Recurrent infantile hypoglycaemia due to combined fructose-1, 6-disphsphatase deficiency and growth hormone deficiency. Pediatr Endocrinol  Metab.7: 1-3

7.      Moon S, Kim JH, Han JH, Ko Sh, Ahn YB, Kim JH, et al. Metabolism.(2011) Novel compound heterozygous mutations in the fructose-1, 6-disphsphatase gene cause hypoglycaemia and lactic acidosis 60(1):107-13

8.      Krishnamurthy V, Eschrich K, Boney A, Sullivan J, McDonald M, Kishnani PS. et al.(2007): Three successful pregnancies through dietary management of fructose-1, 6-bisphsphatase deficiencyJ. Inherit Metab Dis.Oct; 30 (5): 819

9.      Iga M, Kimura M, Ohura T,  Kikawa Y, Yamaguchi S. (2000): Rapid simplified and sensitive method for screening of fructose-1, 6-disphsphatase deficiency by analyzing urinary metabolites in urease/direct preparations and gas chromatographymass spectrometry in the selected-ion monitoring mode. J. Chromatography B Biomed SciApp.746 (1):75-82

10. Ning C, Kuhara T and Matsumoto I. (1997): Chemical diagnosis and metabolic studies for Inborn errors of Carbohydrates Metabolism by GC/MS simultaneous urinary analysisJ. Kanazawa Med. Univ.22:163-171

Dr Vrushali S. Joshi

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