Introduction:
Benign fructosuria is a group of inherited disorders of fructose metabolism. Essential fructosuria is a disorder that may not require treatment, while hereditary fructose intolerance and hereditary fructose-1,6- bisphosphatase deficiency must be taken into account and treated carefully. It is also known as fructose-1-phosphate aldolase deficiency and fructosemia. Fructosuria means the presence of fructose in urine.
What Are the Types of Impaired Fructose Metabolism?
Three categories of genetic disorders have been recognized that result in impaired fructose metabolism. They are:
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Essential fructosuria.
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Hereditary fructose intolerance or HFI.
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Hereditary fructose-1,6-bisphosphatase deficiency.
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Hereditary Fructose Intolerance (HFI).
HFI is the inability of the body to process fructose or the precursors from which fructose (fruit sugar) is derived, such as sugar, brown sugar, and sorbitol. Fructose is a form of sugar that is naturally occurring in food. HFI occurs due to the deficiency of the enzyme fructose-1-phosphate aldolase. This leads to the accumulation of fructose-1-phosphate in the liver, small intestine, and kidney. This could be life-threatening in infants, and the severity ranges from mild to severe in adults.
Patients suffering from hereditary fructose intolerance develop a strong dislike for fruits and sweets. This is a result of the symptoms they suffer after consuming food containing fructose. They experience symptoms such as vomiting, abdominal pain, and low blood sugar.
What Are the Symptoms of HFI?
The symptoms are apparent as soon as a fructose-containing diet is added to an infant with HFI. They include:
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Prolonged vomiting.
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Failure to thrive.
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Growth retardation.
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An episode of unconsciousness.
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Enlargement of the liver.
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Gastrointestinal bleeding as a result of deficiency of clotting factors.
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Increased level of fructose in blood and urine.
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Blood glucose and phosphate levels decrease.
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These patients may exhibit a delay in growth and may suffer from malnutrition. However, there is no evidence of intellectual impairment.
Early diagnosis is crucial in this disease, as adopting a fructose-free diet can help patients with HFI lead a normal life. However, if left untreated, these patients may develop permanent physical harm such as liver, small intestine, and kidney damage.
What Are the Causes of HFI?
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Hereditary fructose intolerance is believed to be an autosomal recessive genetic disorder and therefore inherited.
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A human possesses 46 chromosomes. It is explained as 23 pairs, out of which 1 through 22 are numbered, and X and Y are designated as sex chromosomes. Each chromosome carries the genetic information of an individual and is located in the nucleus of human cells. Males have one of X and one Y chromosomes, while females have two X chromosomes.
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A genetic disorder is determined or passed on to the offspring by the combination of genes received from the father and mother for a particular trait. A recessive genetic disorder occurs when parents transfer a faulty or abnormal gene to the child. A recessive disorder is only expressed when both the pairs of chromosomes are faulty in a person; if a person has only one gene that is faulty and the other one is normal, he is said to be a carrier and will not show any symptoms.
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If both parents are carriers, then there is a 25 % chance of the child being affected in each pregnancy and a 50 % chance of having a carrier child with each pregnancy and a 25 % chance of having an unaffected child with each pregnancy. Parents who are close relatives have a higher chance of carrying an abnormal gene than unrelated parents. Therefore these children have a higher chance of having a genetic disorder.
Who Are Affected By Hereditary Fructose Intolerance?
There is an equal predilection for both males and females to be affected. Hereditary fructose intolerance could be diagnosed at birth or after the child is weaned. It is a rare disorder with an estimated incidence of 1:10,000 to 1: 100,000 births.
How Is Hereditary Fructose Intolerance Diagnosed?
Hereditary fructose intolerance is confirmed by two tests: a fructose tolerance test and an enzyme assay test.
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Enzyme Assay: It requires a liver biopsy to determine the level of aldolase activity.
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Fructose Tolerance Test: It is done by monitoring the patient’s response to intravenous fructose feeding.
However, these tests should be done carefully, especially for a newborn. A non-invasive DNA test is therefore being recommended now. Early diagnosis is the crucial step in treatment. A fructose-free diet helps the patient to lead a normal life. The early diagnosis helps prevent permanent physical damage from occurring to the individual.
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Essential Fructosuria:
Essential fructosuria is the presence of fructose in urine after ingesting fructose. It is a benign autosomal recessive disorder. The deficiency of the fructokinase enzyme in the liver gives rise to this condition. Since this enzyme is the first step in the breakdown of fructose in the liver, which leads to the incomplete metabolism of fructose in the liver, resulting in its excretion in urine, it can be excreted unchanged through the urine, or it may undergo an alternate pathway for excretion; therefore it does not cause any clinical symptoms. It is a mild condition and may not be diagnosed due to the absence of clinical symptoms. It is a benign inborn error of fructose metabolism.
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Hereditary Fructose-1,6- bisphosphatase Deficiency:
Hereditary fructose-1,6- bisphosphatase deficiency interferes and interrupts the ability of the liver to metabolize glycogen. Glycogen is a chemical that stores the body’s energy reserves. If this is not metabolized, the body exhibits signs of low blood sugar (hypoglycemia), hyperventilation, breathing difficulties (apnea), ketosis (a result of incomplete sugar metabolism), and lactic acidosis. These problems, if not promptly recognized and treated, can be life-threatening in newborns. This deficiency compromises gluconeogenesis and results in low blood sugar levels. It is an autosomal recessive disorder. Febrile illness can trigger it.
Conclusion:
Fructose metabolism impairment is a group of inherited disorders that can result in an improper breakdown of fructose and, thereafter, its excretion through the urine. This leads to a decrease in the level of glucose in the blood, as the body is unable to utilize fructose to produce glucose. Essential fructosuria, hereditary fructose-1,6- bisphosphatase deficiency, and hereditary fructose intolerance are the types of fructose metabolism disorders. While the former is mostly asymptomatic, the latter two disorders may need intervention to prevent permanent damage. However, a fructose-free diet can help prevent symptoms.
