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.

• Pallor

  The most frequent clinical findings were hepatomegaly (18X), pallor (14X), haemorrhages (13X). Ascites, oliguria, tachypnoea, fever, splenomegaly and rickets were less frequent. [ncbi.nlm.nih.gov]

  These sweeteners are not common in formulas used today. [5] Symptoms such as vomiting, nausea, restlessness, pallor, sweating, trembling and lethargy can also first present in infants when they are introduced to fruits and vegetables. [en.wikipedia.org]

  The patient was a healthy, breastfed infant; however, in his fourth month he developed an acute episode of repetitive vomiting, irritability, pallor, and shock. [pediatrics.aappublications.org]

  The result is pallor, sweating, trembling, fear, convulsions and ultimately loss of consciousness because the brain cannot tolerate being deprived of glucose. [independent.co.uk]

• Fever

  Ascites, oliguria, tachypnoea, fever, splenomegaly and rickets were less frequent. Laboratory findings were indicative of disturbed hepatic and renal tubular function and also of disturbed intermediary metabolism (hypokaliaemia, hypophosphataemia). [ncbi.nlm.nih.gov]

  Initial symptoms include severe abdominal pain, vomiting that can lead to dehydration, and unexplained fever. Other symptoms include extreme thirst and excessive urination and sweating. There is also a loss of appetite and a failure to grow. [healthofchildren.com]

  Initial symptoms include vomiting, dehydration, and unexplained fever. Other symptoms include extreme thirst and excessive urination and sweating. There will also be a loss of appetite and a failure to grow. [medical-dictionary.thefreedictionary.com]

  Tell-tale signs are skin rashes, hives, itching, a runny nose at mealtimes, asthma and hay fever. Lactose and fructose intolerance co-exist in approximately 20-30% of individuals. [foodintolerances.org]

• Unconsciousness

  Herein we report on a case of hereditary fructose intolerance with initial presentation of episodic unconsciousness, seizure, hypoglycemia, hepatomegaly, and abnormal liver function since the patient was 11 months old. [ncbi.nlm.nih.gov]

  While it is acceptable for sufferers to eat the lactose in milk, and pure glucose, anything containing fructose - sugar in tea, cake, even an apple - can cause severe stomach pains, even convulsions and unconsciousness. [independent.co.uk]

  […] glucagon injection (a medication used in an emergency to increase blood glucose) and seek emergent treatment when the child has the following symptoms: inability to swallow numbness in mouth or tongue poor coordination poor concentration, confusion unconsciousness [healthofchildren.com]

• Death in Infancy

  Without treatment and continued ingestion of fructose, individuals may have worsening symptoms and early death in infancy. [evolvegene.com]

• Vomiting

  We report on an infant with suspected HFI who presented with repeated episodes of vomiting and hypotension after ingestion of fruit-containing meals. The first episode occurred at age 4 months. [ncbi.nlm.nih.gov]

  Infants will present with feeding difficulties, vomiting, failure to thrive and symptoms of hypoglycemia and acidosis. [symptoma.com]

  Vomiting and hypoglycemia follow intake of fructose. [medical-dictionary.thefreedictionary.com]

  The patient was a healthy, breastfed infant; however, in his fourth month he developed an acute episode of repetitive vomiting, irritability, pallor, and shock. [pediatrics.aappublications.org]

• Nausea

  In HFI, fructose ingestion generally induces gastro-intestinal (nausea and vomiting, abdominal pain, meteorism) and hypoglycemic symptoms. Fasting is well tolerated. [ncbi.nlm.nih.gov]

  The following are observed: HFI is asymptomatic in nature, before the intake of fructose Initial signs include diarrhea, vomiting, nausea, swollen abdomen with pain, hypoglycemia (low blood sugar). [dovemed.com]

  Common Features of the Disorder Failure to thrive in infancy Nausea Bloating Abdominal pain Diarrhea Vomiting Low blood sugar Jaundice Enlarged liver Liver disease (i.e. cirrhosis) Seizures Coma Growth delays Kidney failure Prognosis Hereditary Fructose [evolvegene.com]

  These sweeteners are not common in formulas used today. [5] Symptoms such as vomiting, nausea, restlessness, pallor, sweating, trembling and lethargy can also first present in infants when they are introduced to fruits and vegetables. [en.wikipedia.org]

• Failure to Thrive

  In the long run, these symptoms will lead to failure to thrive. [symptoma.com]

  Symptoms are present only after the ingestion of fructose, which leads to brisk hypoglycemia, and an individual with continued ingestion will exhibit vomiting, abdominal pain, failure to thrive, and renal and liver failure. [ncbi.nlm.nih.gov]

  All these symptoms of vomiting, lethargy, failure to thrive, hypoglycemia and liver failure are characteristic of this disease. [namrata.co]

• Food Intolerance

  On the Food Intolerance Network website we will use the term "fructose malabsorption", and sometimes "fructose intolerance", but in that case we never talk about hereditary fructose intolerance (HFI) unless this is referred to specifically! [food-intolerance-network.com]

  Food Allergies and Food Intolerance: The Complete Guide to Their Identification and Treatment. Rochester, VT: Inner Traditions International, 2000. David, T. J. Food and Food Additive Intolerance in Childhood. [healthofchildren.com]

  Explain your fructose intolerance in brief terms and order only foods that you know cannot have sugars and how they should be prepared. [diet.com]

• Recurrent Vomiting

  Clinical description HFI usually presents in infancy at the time of weaning (when fructose is added to the diet), manifesting with hypoglycemia, lactic acidosis, ketosis with recurrent vomiting, abdominal pain and systemic manifestations following consumption [orpha.net]

  Clinical features include-Recurrent vomiting, abdominal pain, and hypoglycemia that may be fatal. [usmle.biochemistryformedics.com]

  Clinical features include- Recurrent vomiting, Abdominal pain, and Hypoglycemia that may be fatal. [namrata.co]

• Hepatomegaly

  He presented with episodic unconsciousness, seizures, hypoglycemia, hepatomegaly and abnormal liver function. [ncbi.nlm.nih.gov]

  As a result of this disorder individuals may have all of the following symptoms except: -reduced blood glucose levels during fasting -reducing sugar in the urine -inability to metabolize lactose -hepatomegaly The metabolic disease, which is resulted due [chegg.com]

• Seizure

  Herein we report on a case of hereditary fructose intolerance with initial presentation of episodic unconsciousness, seizure, hypoglycemia, hepatomegaly, and abnormal liver function since the patient was 11 months old. [ncbi.nlm.nih.gov]

  Ingesting more than tiny amounts of fructose or sucrose causes low blood sugar levels (hypoglycemia), with sweating, confusion, and sometimes seizures and coma. [merckmanuals.com]

  Some infants have a more severe reaction to such sugars with lethargy, seizures and coma. Older children and adults develop a protective aversion to fruits and sweets. [disorders.eyes.arizona.edu]

• Irritability

  Mots clés : Vitamine C, Hypoglycémie, Intolérance héréditaire au fructose, Intestin irritable, Goutte Keywords: Vitamin C, Hypoglycemia, Hereditary fructose intolerance, Irritable bowel, Gout The full text of this article is available in PDF format. [em-consulte.com]

  Moreover, hypoglycemia induced by fructose absorption, unexplained liver disease, irritable bowel syndrome or familial gout in an adult is suggestive of the diagnosis. [ncbi.nlm.nih.gov]

  /sucrose-containing foods Doing well after eating foods without fructose/sucrose The early symptoms of fructose intolerance may resemble those of galactosemia: irritability, jaundice, vomiting, convulsions and an enlarged liver and spleen. [foodreactions.co.uk]

  It can arise with various diseases of the gut where different types of nutrients may act as irritants. [healthhype.com]

• Confusion

  Ingesting more than tiny amounts of fructose or sucrose causes low blood sugar levels (hypoglycemia), with sweating, confusion, and sometimes seizures and coma. [merckmanuals.com]

  I mention this because, even removing FM and HFI from your search, fructose is plastered everywhere, just adding to the confusion. [thefriendlygourmand.com]

• Lethargy

  Because this non-immunoglobulin E-mediated gastrointestinal food hypersensitivity manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy, it may be misinterpreted as HFI. [ncbi.nlm.nih.gov]

  Case details A 3-year-old boy was brought to the emergency department after several episodes of vomiting and lethargy. [namrata.co]

  Some infants have a more severe reaction to such sugars with lethargy, seizures and coma. Older children and adults develop a protective aversion to fruits and sweets. [disorders.eyes.arizona.edu]

  These sweeteners are not common in formulas used today. [5] Symptoms such as vomiting, nausea, restlessness, pallor, sweating, trembling and lethargy can also first present in infants when they are introduced to fruits and vegetables. [en.wikipedia.org]

  Infants are healthy until they ingest fructose; fructose 1-phosphate then accumulates, causing hypoglycemia, nausea and vomiting, abdominal pain, sweating, tremors, confusion, lethargy, seizures, and coma. [merckmanuals.com]

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.

• Liver Biopsy

  A second liver biopsy 10 months later had normal aldolase B activity towards fructose-1-phosphate and a fructose tolerance test was also normal. A possible explanation for these findings is proposed. [ncbi.nlm.nih.gov]

Treatment currently relies solely on dietary restriction of problematic sugars. [ncbi.nlm.nih.gov]

Treatment Treatment for Hereditary Fructose Intolerance involves lifelong dietary restriction of fructose and other sugary substances (i.e. sucrose). Early diagnosis and treatment can prevent the symptoms of Hereditary Fructose Intolerance. [evolvegene.com]

[ edit ] Treatment of HFI depends on the stage of the disease, and the severity of the symptoms. [en.wikipedia.org]

Treatment Treatment Options: Treatment with a fructose restricted diet is highly effective but must be strictly enforced to allow normal growth. References Ananth N, Praveenkumar GS, Rao KA, Vasanthi, Kakkilaya S. [disorders.eyes.arizona.edu]

Intensive care and supportive measures may be required in case of acute intoxication Prognosis HFI prognosis is favorable with normal growth, intelligence and lifespan. [orpha.net]

The prognosis depends on how soon the fructose intolerance diagnosis was made, how quickly fructose and sucrose are removed from the diet and the severity of the condition, according to Medline Plus. [healthyeating.sfgate.com]

Intolerance has a favorable prognosis with treatment. [evolvegene.com]

We also performed a review of the literature on the different etiologies of elevated lysosomal enzyme activities in serum or plasma. © 2016 Wiley Periodicals, Inc. [ncbi.nlm.nih.gov]

Etiology HFI is caused by mutations in the ALDOB (9q22.3) gene, encoding the enzyme aldolase B. [orpha.net]

(Etiology) Hereditary Fructose Intolerance is caused by inheriting an autosomal recessive gene, which lies on chromosome 9 and is defective The problem gene (known as ALDOB), disturbs or changes the normal and physiologically programmed production of [dovemed.com]

Summary Epidemiology The estimated prevalence is 1 in 20,000 in Europe and the carrier frequency is about 1 in 70. The prevalence of HFI in adult population is not known. [orpha.net]

Epidemiology Frequency United States Although the true prevalence has not been established, hereditary fructose intolerance may be more common than originally believed; many asymptomatic affected people may simply avoid the ingestion of most or all sweets [reference.medscape.com]

Pathophysiologic classification of lactic acidosis. [reference.medscape.com]

The potential toxic effects of fructose in humans also are discussed: it is essential to understand these toxic effects in order to comprehend the pathophysiology of hereditary fructose intolerance and of fructose 1,6-bisphosphatase deficiency. ... [ommbid.mhmedical.com]

Pathophysiology A defect in the Aldolase B gene results in a decrease in activity that is 15 percent or less than that of normal. This results in a buildup of F1P levels in the hepatocytes. [namrata.co]

J Cell Physiol 209:701-705 Google Scholar Gitzelmann R (1995) Galactose-1-phosphate in the pathophysiology of galactosemia. [link.springer.com]

This is to prevent serious harm from occurring, during the child’s most critical formative phase. [dovemed.com]

Those who survive childhood learn to avoid sweets, effectively preventing further symptoms and complications. The disease is caused by a genetically defective hepatic enzyme, aldolase B. [ncbi.nlm.nih.gov]

Prevention Couples with a family history of fructose intolerance who wish to have a baby may consider genetic counseling. Most of the damaging effects of the disease can be prevented by sticking to a fructose-free diet. [nicklauschildrens.org]

1. Baerlocher K, Gitzelmann R, Steinmann B, Gitzelmann-Cumarasamy N. Hereditary fructose intolerance in early childhood: a major diagnostic challenge. Survey of 20 symptomatic cases. Helv Paediatr Acta. 1978;33:465–487
2. Odièvre M, Gentil C, Gautier M, Alagille D. Hereditary fructose intolerance in childhood. Diagnosis, management, and course in 55 patients. Am J Dis Child. 1978 Jun;132(6):605-608.
3. Ali M, Rellos P, Cox TM. Hereditary fructose intolerance. J Med Genet. 1998;35:353–65.
4. Steinmann B, Santer R. Disorders of fructose metabolism. In: Saudubray JM, van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. Berlin: Springer-Verlag; 2012;157–165.
5. Steinmann B, Gitzelmann R. The diagnosis of hereditary fructose intolerance. Helv Paediatr Acta. 1981;36:297–316
6. Bouteldja N, Timson DJ. The biochemical basis of hereditary fructose intolerance. J Inherit Metab Dis. 2010 Apr;33(2):105-12
7. Steinman B, Gitzelmann R, van den Berghe G. Disorders of fructose metabolism. In: Scriver CR, Beaudet AL, Valle D, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2001;1489–1520.
8. Tolan DR. Molecular basis of hereditary fructose intolerance: Mutations and polymorphisms in the human aldolase B gene. Hum. Mutat. 1995;6:210–218.
9. James CL, Rellos P, Ali M, Heeley AF, Cox TM. Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population. J Med Genet. 1996;33(10):837-41.
10. Ferri L, Caciotti A, Cavicchi C, Rigoldi M, et al. Integration of PCR-sequencing analysis with multiplex ligation-dependent probe amplification for diagnosis of hereditary fructose intolerance. JIMD Rep. 2012;6:31-7.
11. Coffee EM, Yerkes L, Ewen EP, Zee T, Tolan DR. Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population. J Inherit Metab Dis. 2010 Feb;33(1):33-42.
12. Morris RC Jr. An experimental renal acidification defect in patients with hereditary fructose intolerance. J Clin Invest. 1968;47:1648–63.