Fructose Intolerance, Hereditary
Synonyms of Fructose Intolerance, Hereditary
- Fructose-1-Phosphate Aldolase Deficiency
- No subdivisions found.
There are three inherited disorders of fructose metabolism that are recognized and characterized. Essential fructosuria, is a mild disorder not requiring treatment, while Hereditary fructose intolerance (HFI) and Hereditary fructose-1,6-biphosphatase deficiency (HFBP) are treatable and controllable but must be taken seriously.
Hereditary Fructose Intolerance (HFI) is an inherited inability to digest fructose (fruit sugar) or its precursors (sugar, sorbitol and brown sugar). This is due to a deficiency of activity of the enzyme fructose-1-phosphate aldolase, resulting in an accumulation of fructose-1-phosphate in the liver, kidney, and small intestine. Fructose is a naturally occurring sugar that is used as a sweetener in many foods, including many baby foods. This disorder can be life threatening in infants and ranges from mild to severe in older children and adults.
People who have HFI usually develop a strong dislike for sweets and fruit. After eating foods containing fructose, they may experience such symptoms as severe abdominal pain, vomiting, and low blood sugar (hypoglycemia).
Early diagnosis is important because, while most people who have HFI can lead normal lives if they adopt a fructose-free diet. If left untreated however, the condition can lead to permanent physical harm, including especially, serious liver and kidney damage.
Soon after fructose is added to the diet of an infant with HFI, symptoms become apparent. These may include prolonged vomiting, failure to thrive, jaundice and growth retardation. There may be occasional episodes of unconsciousness. Other symptoms include enlargement of the liver and frequently cirrhosis, and a tendency towards gastrointestinal bleeding because of deficiency of clotting factors. There are decreased levels of glucose and phosphate in the blood and increased levels of fructose in the blood and urine.
Patients with Hereditary Fructose Intolerance usually develop a strong dislike for sweets and fruit. Although infants may exhibit growth delays and even experience malnutrition, there is no intellectual impairment.
It is very important to recognize the intolerance early to avoid damage to the liver, kidney, and small intestine.
Studies of families in which HFI occurs leads geneticists to believe that the disorder is inherited as an autosomal recessive trait, The responsible gene has been mapped to the long arm (q) of chromosome 9 at gene map locus 9q22.3.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 9q22.3" refers to band 22.3 on the long (q) arm of chromosome 9. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Hereditary Fructose Intolerance may be diagnosed at birth or shortly thereafter when the infant is weaned. Like other autosomal disorders it is equally distributed among males and females. Estimates of the incidence of the disorder range widely from 1:10,000 to 1:100,000 births.
Essential Fructosuria is characterized by the presence of fructose in the urine after ingesting fructose. It arises as a result of a deficiency of the hepatic enzyme fructokinase and is an autosomal recessive genetic disorder. The disorder is mild and it probably remains undiagnosed in many, many people.
Hereditary fructose-1,6-biphosphatase deficiency interferes with and even interrupts the ability of the liver and other organs to metabolize glycogen, which is a chemical that stores the body's energy reserves. As a consequence, the patient shows signs of hypoglycemia (low blood sugar), breathing difficulties (apnea), hyperventilation, ketosis (a sign of incomplete sugar metabolism) and lactic acidosis. These problems can be life threatening in newborns if left untreated.
A diagnosis of HFI can be definitively confirmed by either of two tests: an enzyme assay, requiring a liver biopsy, to determine the level of aldolase activity or a fructose tolerance test in which the patient's response to intravenous fructose feeding is carefully monitored. It should be carefully noted, however, that each of these tests carries with it a substantial risk, especially to a newborn child. A non-invasive DNA test is increasingly being recommended instead.
The standard therapy is a fructose-free diet. As long as patients with Hereditary Fructose Intolerance do not ingest fructose, they can lead normal lives. However, it is important that this disorder be diagnosed early, and the special diet adopted, to prevent permanent physical damage.
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