Hereditary Fructose Intolerance

Patients suffering from HFI develop and grow normally while being only breastfed. Problems usually start to appear at the time of weaning, when fructose is first introduced into the diet through foods containing fructose, sucrose (a disaccharide containing glucose and fructose units), or sorbitol. Consumption of fructose-containing foods results in hypoglycemia, lactic acidosis, and ketosis and causes difficulties in feeding, repeated vomiting, and abdominal discomfort. In the long run, these symptoms will lead to failure to thrive. Continued feeding with sugars that either contain fructose or are converted to fructose may lead to liver and kidney failure, convulsions, coma, and possibly death [1] [2] unless the problem is addressed.

Patients who live beyond infancy develop a strong dislike for foods containing fructose, mainly fruits and sweets, and continue to have unfavorable reactions (vomiting and hypoglycemia) following fructose ingestion throughout the rest of their lives. In general, there is very little tooth decay in adults with HFI, which, in itself, may be an indication of the disease, and is probably due to the voluntary exclusion of sweets from their diet.

Taking a detailed dietary history in individuals suspected of hereditary fructose intolerance is a crucial component of diagnosis. Infants will present with feeding difficulties, vomiting, failure to thrive [1] and symptoms of hypoglycemia and acidosis [3]. In older children and adults, the history is expected to show episodes of food refusal: affected infants and children will recoil from sweets after being taken ill several times. Sometimes, apparently healthy adults are given a diagnosis of HFI based on dietary history. As mentioned, a complete lack of tooth decay can also serve as an indicator for hereditary fructose intolerance.

A comprehensive history has to be followed up with laboratory tests and physical examination. There are several tests to verify suspected HFI, i.e. fructose 1-phosphate aldolase deficiency: one test determines if there is a reducing sugar in the urine that is not glucose. Reducing sugars are easily detected with Clinitest; if this is positive, the identity of the sugar can be established by further tests, such as thin-layer chromatography or enzyme assays [4]. Another test is the measurement of the aldolase enzyme activity in liver or intestinal mucosal biopsies: the enzyme’s function is impaired in HFI patients [5]. The latter test has been, to a large extent, superseded by molecular methods, which are non-invasive. DNA analysis can be performed using leukocytes. Sequencing of the aldolase gene (located on chromosome 9) will, in all probability, diagnose the disease and unambiguously identify the mutation responsible for it [6] [7] [8 [9] [10] [11]. These tests can define the mutational spectrum and can serve as the basis for designing targeted mutational tests [11].

The intravenous fructose tolerance test [5] is also non-invasive but has to be performed in a controlled hospital environment because of the hazards associated with fructose administration to HFI patients [1] [3]. Oral fructose tolerance testing should not be used because of the danger of severe gastrointestinal reaction. Observing relief of symptoms in response to the dietary exclusion of fructose also has strong diagnostic value.

Hepatic function tests should be performed to evaluate whether the liver is damaged. Patients, who do not receive treatment, usually show indications of hepatocellular injury, which may not be reversible [2]; the histology shows multiple abnormalities, such as fatty deposits in peripheral lobules. Except in cases where there is strong evidence for liver disease, liver biopsy should not be used for diagnosis.

Urine tests may show elevated levels of glucose, proteins, and amino acids, characteristic of renal Fanconi syndrome, which may be caused by fructose intolerance. Decreased tubular reabsorption of bicarbonate [12] lowers the blood bicarbonate concentration and contributes to metabolic acidosis. To test for tubular acidosis, plasma electrolyte levels should be determined.

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