Fructose intolerance (Fructosemia) (Hereditary fructose intolerance) - Gen ALDOB.
The fructose intolerance or fructosemia, is a metabolic disease autosomal recessive, characterized by fructose intolerance due to deficiency of aldolase B, primary enzyme fructose metabolism, localized mainly in the liver, and also in kidneys and small intestine. The clinical consequences of fructose intolerance are revealed when sucrose or fructose are added to the diet, leading to nausea, bloating and abdominal pain, vomiting, diarrhea, liver failure and hypoglycemia. Repeated ingestion of foods containing fructose can lead to liver damage and kidney. Liver damage can cause jaundice, hepatomegaly and cirrhosis. Continued exposure to fructose can cause lethargy, convulsions, coma , and death from liver and kidney failure.
Fructose intolerance should not be confused with a condition called fructose malabsorption. In people with this condition, cells of the intestine can not absorb fructose normally, resulting in bloating, diarrhea or constipation, flatulence and stomachache. Fructose malabsorption affects approximately 40% of people in the Western Hemisphere. Its cause is unknown.
This process is due to mutations in the gene ALDOB, 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 metabolism of fructose for energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down fructose molecule - 1-phosphate and dihydroxyacetone phosphate in glyceraldehyde. To a lesser extent, the enzyme is also involved in glucose metabolism.
There are more than 50 genetic abnormalities in the gene ALDOB cause fructose intolerance (fructosemia). Most of them consist of nucleotide substitutions involving amino acid changes that affect the stability of the enzyme or its catalytic activity, which prevents proper metabolism of fructose, sucrose and sorbitol. A mutation, found in about half of those affected, replaces the amino acid alanine by the amino acid proline at position 149 of the enzyme (Ala149Pro or A149P). This mutation alters the three dimensional form of the enzyme. Altering the shape of the enzyme makes it difficult for aldolase enzyme molecule B join together and form tetramers. If the molecules do not form a tetramer, aldolase B can not metabolize fructose. Other mutations consist of deletions in the gene ALDOB. Aldolase A deficiency of functional B causes an accumulation of fructose 1-phosphate in the liver cells. This accumulation is toxic, so eventually die of liver cells. In addition, degradation products of fructose 1-phosphate are required in the body to produce energy and maintain blood glucose concentrations. The combination of a decrease in cellular energy available, a low concentration of glucose in the blood and death of liver cells causing the characteristics of fructose intolerance. These individuals, manifest, therefore fructose toxicity can cause serious damage, which can become lethal. On the other hand, if the condition diagnosed early and properly treated it is a relatively benign disease.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with fructose intolerance (fructosemia), by complete PCR amplification of exons ALDOB gene, and subsequent sequencing. The most frequent mutations 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, will have to continue the study the other six exons, thus reducing completion time and cost.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).