Fructosemia (Hereditary fructose intolerance) - ALDOB gene
Fructose intolerance or fructosemia is an autosomal recessive metabolic disease, characterized by fructose intolerance as a result of deficiency of aldolase B, the main enzyme of fructose metabolism, located mainly in the liver, and also in kidneys and small intestine. The clinical consequences of fructose intolerance become apparent when sucrose, or fructose, is added to the diet, resulting in nausea, bloating and abdominal pain, vomiting, diarrhea, liver failure and hypoglycemia. Repeated ingestion of foods containing fructose can lead to liver and kidney damage. Liver damage can cause jaundice, hepatomegaly and cirrhosis. Continued exposure to fructose can cause seizures, coma and ultimately death from liver and kidney failure.
Fructose intolerance should not be confused with a disease called fructose malabsorption. In people with this disorder, intestine cells cannot absorb fructose normally, leading to swelling, diarrhea or constipation, flatulence and stomach pain. Fructose malabsorption affects approximately 40% of people in the Western Hemisphere. Its cause is unknown.
This process is due to mutations in the ALDOB gene, located on the long arm of chromosome 9 (9q22.3). This gene encodes the enzyme aldolase B. This enzyme is found mainly in the liver and is involved in the metabolization of fructose for energy. Aldolase B is responsible for the second stage in fructose metabolism, which breaks down the fructose-1-phosphate molecule into glyceraldehyde and dihydroxyacetone phosphate. To a lesser extent, the enzyme is also involved in glucose metabolization.
More than 50 genetic abnormalities in the ALDOB gene that cause fructose intolerance (fructosemia) have been identified. Most of them consist of nucleotide substitutions that involve amino acid changes that affect the stability of the enzyme or its catalytic activity, which prevents the correct metabolization of fructose, sucrose and sorbitol. A mutation, found in approximately half of the affected people, replaces the amino acid alanine with the proline amino acid at position 149 of the enzyme (Ala149Pro or A149P). This mutation alters the 3-dimensional form of the enzyme. Altering the shape of the enzyme makes it difficult for aldolase B enzyme molecules that bind together and form tetramers. If the molecules do not form a tetramer, aldolase B cannot metabolize fructose. Other mutations consist of deletions in the ALDOB gene. A deficiency of functional aldolase B causes an accumulation of fructose-1-phosphate in liver cells. This accumulation is toxic, so that liver cells eventually die. In addition, degradation products of fructose-1-phosphate are necessary in the body to produce energy and maintain blood glucose concentrations. The combination of a decrease in available cellular energy, a low concentration of blood glucose and the death of liver cells causes the characteristics of fructose intolerance. These individuals, therefore, show fructose toxicity and can cause serious damage, which can be lethal. On the other hand, if the pathology is diagnosed early and receives the appropriate treatment, it constitutes a relatively benign disease.
This disease is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have mutations for the alteration to be 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 detect mutations associated with fructose intolerance (fructosemia), by complete PCR amplification of the exons of the ALDOB gene, and subsequent sequencing. The most frequent mutations are found in exons 5 (A149P and A174D) and 8 (N334A), so we offer the possibility of starting the test with these two exons and, if found, do not have to continue with the study of the other six exons, with the consequent reduction of realization time and cost.
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).