Fructose 1,6-bisphosphatase deficiency is a disorder characterized by deficiency of activity of fructose 1,6-bisphophatase (FDPase), a key enzyme in gluconeogenesis. Gluconeogeneis is a process by which endogenous glucose is produced from non-carbohydrate sources, including gluconeogenic amino acids, glycerol, or lactate. This is a key activity in maintaining glucose homeostasis in the body. Patients with FDPase deficiency show typical signs and symptoms of hypoglycemia and metabolic acidosis following fructose ingestion or infections in the neonatal period. These signs and symptoms include hunger, irritability, light-headedness, fatigue, lethargy, seizures, loss of consciousness, trembling, and even tachycardia, and hypertension.
The most common and easily available diagnostic test for FDPase deficiency is a D-fructose challenge. Patients are given fructose during a period of fasting, and low glucose levels and high lactate levels are diagnostic of FDPase deficiency. However, this test is dangerous and close monitoring is required, since it may end up with the patient becoming hypoglycemic and developing metabolic acidosis, and causing fatal hepatic or renal injury. The most specific and safe diagnostic test remains direct enzymatic assay of hepatic FDPase activity via a needle biopsy. However, this requires a highly specialized procedure that may not be easily available. The condition can be managed by practicing a complete avoidance of fructose and its cognate sugars like sorbitol. Prolonged fasting should also be avoided. Early diagnosis of the disorder is critical, since unmanaged FDPase deficiency can result in damage to the brain, kidneys, and/or liver. With early diagnosis and proper management, prognosis is good. FDPase deficiency is a rare disorder, affecting 1 in 20,000 newborns worldwide.
Al Raqum and Fayka (1994) described two brothers with FDPase Deficiency. The condition was confirmed by leukocyte enzyme assay.
Prahl et al. (2006) described a family from Morocco with parental consanguinity with three affected children. All were homozygous for a novel mutation in exon 5: 685 C>T of the gene coding for the liver isoform of fructose 1,6-bisphosphatase (FBP1).
Faiyaz-Ul-Haque et al. (2009) studied five consanguineous Arab families, in which 17 patients were clinically diagnosed with FBP deficiency. The five families originated from different regions of the country. Pedigree analyses suggested an autosomal recessive mode of inheritance.