Fructose-1,6-bisphosphatase deficiency (FBP1D) - FBP1 and FBP2 genes.

Fructose-1,6-bisphosphatase deficiency is a process that involves significant alterations in gluconeogenesis and is characterized by repeated episodes of hypoglycaemia, hyperventilation, apnea, ketosis and metabolic acidosis, and is frequently fatal in the neonatal period and the childhood. However, once the diagnosis is made, the progression of the disease is relatively optimal. The excretion of glycerol in urine can help differentiate fructose-1,6-biphosphatase deficiency from other metabolic errors with similar symptoms.

Fructose 1,6-bisphosphatase (FBPase) is a key enzyme in gluconeogenesis, as it acts by catalyzing the cleavage of fructose-1,6-bisphosphate in fructose-6-phosphate and inorganic phosphate. FBPases are encoded by two genes, FBP1 and FBP2. The FBP1 gene (fructose-bisphosphatase 1), located on the long arm of chromosome 9 (9q22.3), encodes fructose-1,6-bisphosphatase 1, a protein of 362 amino acids, located in the liver. This enzyme acts as a speed-limiting enzyme in gluconeogenesis, plays a role in the regulation of glucose detection and insulin secretion from pancreatic beta cells. In addition, it seems to modulate gluconeogenesis of glycerol in the liver, it is an important regulator of appetite and adiposity. The FBP2 gene encodes a protein of 339 amino acids, located mainly in the muscle, and with a sequence identity of 77% with FBP1. However, the problems derived from the deficiency of fructose-1,6-bisphosphatase are due to mutations located in the FBP1 gene.

Until a few years ago, this disease could only be diagnosed by determining the enzymatic activity in samples from liver biopsies. Today, molecular analysis provides us with a more efficient and accurate diagnostic method. At least eleven mutations that alter the enzymatic activity of FBPase have been detected, including amino acid changes, alteration of the reading pattern, insertions, deletions, alteration of highly conserved domains, etc., that induce this type of metabolic alteration. Some of the genetic changes identified in patients with deficiency of fructose-1,6-bisphosphatase include 960insG, G164S, A177D, E30X, F194S and P284R.

The deficiency of fructose-1,6-bisphosphatase is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have the mutations so that the alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Fructose-1,6-biphosphatase, by means of the complete PCR amplification of the exons of the FBP1 and FBP2 genes, respectively, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).