Daily Fructose Traces Intake and Liver Injury in Children with Hereditary Fructose Intolerance.

BACKGROUND: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. METHODS: Patients' clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. RESULTS: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransferrin percentage (R2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R2 0.5, p = 0.0001). p.A150P homozygous patients had lower ALT values at diagnosis than p.A175D variant homozygotes cases (58 ± 55 IU/L vs. 143 ± 90 IU/L, p = 0.01). CONCLUSION: A group of HFI patients on FSS-free diet presented persistent mild hypertransaminasemia which did not correlate with fructose intake. Genotypes may influence serum liver enzyme levels. CDT profile represents a good marker to assess FSS intake.

Predictors of response to a low-FODMAP diet in patients with functional gastrointestinal disorders and lactose or fructose intolerance.

BACKGROUND: Diets low in fermentable sugars (low-FODMAP diets) are increasingly adopted by patients with functional gastrointestinal disorders (FGID), but outcome predictors are unclear. AIM: To identify factors predictive of an efficacious response to a low-FODMAP diet in FGID patients with fructose or lactose intolerance thereby gaining insights into underlying mechanisms. METHODS: Fructose and lactose breath tests were performed in FGID patients to determine intolerance (positive symptom score) and malabsorption (increased hydrogen or methane concentrations). Patients with fructose or lactose intolerance consumed a low-FODMAP diet and global adequate symptom relief was assessed after 6-8 weeks and correlated with pre-diet clinical symptoms and breath test results. RESULTS: A total of 81% of 584 patients completing the low-FODMAP diet achieved adequate relief, without significant differences between FGID subgroups or types of intolerance. Univariate analysis yielded predictive factors in fructose intolerance (chronic diarrhoea and pruritus, peak methane concentrations and fullness during breath tests) and lactose intolerance (peak hydrogen and methane concentrations and flatulence during breath tests). Using multivariate analysis, symptom relief was independently and positively predicted in fructose intolerance by chronic diarrhoea [odds ratio (95% confidence intervals): 2.62 (1.31-5.27), P = 0.007] and peak breath methane concentrations [1.53 (1.02-2.29), P = 0.042], and negatively predicted by chronic nausea [0.33 (0.16-0.67), P = 0.002]. No independent predictive factors emerged for lactose intolerance. CONCLUSIONS: Adequate global symptom relief was achieved with a low-FODMAP diet in a large majority of functional gastrointestinal disorders patients with fructose or lactose intolerance. Independent predictors of a satisfactory dietary outcome were only seen in fructose intolerant patients, and were indicative of changes in intestinal host or microbiome metabolism.

Relapsing Acute Axonal Neuropathy in Hereditary Fructose Intolerance.

BACKGROUND: A severe neurological abnormality has not been previously described in individuals with hereditary fructose intolerance, which typically presents early in childhood with severe metabolic acidosis and hypoglycemia. PATIENT DESCRIPTION: We describe a boy who by age five years had required multiple admissions to the pediatric intensive care unit for an aggressive and atypical, relapsing and remitting neuropathy with features of acute motor axonal neuropathy (AMAN). It was later discovered that he also had undiagnosed hereditary fructose intolerance, and the severity and frequency of his neurological episodes diminished following an exclusion diet. His asymptomatic younger brother was diagnosed with hereditary fructose intolerance on screening. He is on a fructose-free diet and has not developed neurological symptoms. CONCLUSIONS: Ongoing low-level exposure to fructose prior to diagnosis may have contributed to our patient's neurological dysfunction. Early diagnosis and treatment may prevent neurological complications of hereditary fructose intolerance.

Dieta pobre en FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) en el síndrome de intestino irritable: indicación y forma de elaboración / Diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the treatment of irritable bowel syndrome: indications and design

En los últimos años está creciendo el interés en la dieta pobre en fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) como pilar importante en el tratamiento del síndrome de intestino irritable (SII). Este modelo de dieta lo desarrolló un equipo multidisciplinar de la Universidad de Monash, en Melbourne, y empezó a ganar notoriedad a partir de la publicación de un estudio en 2008 que demostraba que los hidratos de carbono fermentables (FODMAPs) de la dieta actuaban como causantes de síntomas en los pacientes con SII. Desde entonces se han llevado a cabo varios ensayos controlados aleatorizados que, aunque con muestras reducidas de pacientes, han vuelto a demostrar las ventajas de este modelo dietético (AU)

In recent years, there has been growing interest in diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) as an important mainstay in the treatment of irritable bowel syndrome (IBS). This model of diet was developed by a multidisciplinary team from the Monash University in Melbourne and became well-known after the publication of a study in 2008 showing that dietary FODMAPs acted as causing factors in patients with IBS. Since then there have been several randomized controlled trials which, although with small sample sizes, have again shown the benefits of this dietary pattern (AU)

Self-reported dietary fructose intolerance in irritable bowel syndrome: Proposed diagnostic criteria.

AIM: To study the criteria for self-reported dietary fructose intolerance (DFI) and to evaluate subjective global assessment (SGA) as outcome measure. METHODS: Irritable bowel syndrome (IBS) patients were randomized in an open study design with a 2 wk run-in on a habitual IBS diet, followed by 12 wk with/without additional fructose-reduced diet (FRD). Daily registrations of stool frequency and consistency, and symptoms on a visual analog scale (VAS) were performed during the first 4 wk. SGA was used for weekly registrations during the whole study period. Provocation with high-fructose diet was done at the end of the registration period. Fructose breath tests (FBTs) were performed. A total of 182 subjects performed the study according to the protocol (88 FRD, 94 controls). RESULTS: We propose a new clinically feasible diagnostic standard for self-reported fructose intolerance. The instrument is based on VAS registrations of symptom relief on FRD combined with symptom aggravation upon provocation with fructose-rich diet. Using these criteria 43 of 77 patients (56%) in the present cohort of IBS patients had self-reported DFI. To improve the concept for clinical evaluation, we translated the SGA scale instrument to Norwegian and validated it in the context of the IBS diet regimen. The validation procedures showed a sensitivity, specificity and κ value for SGA detecting the self-reported DFI group by FRD response within the IBS patients of 0.79, 0.75 and 0.53, respectively. Addition of the provocation test yielded values of 0.84, 0.76 and 0.61, respectively. The corresponding validation results for FBT were 0.57, 0.34 and -0.13, respectively. CONCLUSION: FRD improves symptoms in a subgroup of IBS patients. A diet trial followed by a provocation test evaluated by SGA can identify most responders to FRD.

Effects of dietary education, followed by a tailored fructose-restricted diet in adults with fructose malabsorption.

OBJECTIVE: Fructose is absorbed by GLUT transporters in the small intestine. If this process is inadequate, abdominal symptoms because of fructose intolerance may arise. The effect of a tailored fructose-restricted diet on gastrointestinal complaints was assessed in patients with fructose intolerance. MATERIALS AND METHODS: Following an abnormal fructose breath test (50 g), 107 patients (64 also with lactose intolerance) entered three study periods: weeks 0-32 (free diet), weeks 32-36 (progressive increasing amount of fructose up to quantity inducing symptoms, 'trigger dose'), and weeks 36-48 (tailored fructose-restricted diet according to the 'trigger dose'). A subgroup of 15 patients underwent additional fructose breath tests (35, 25 g) to compare three different doses. RESULTS: At baseline, the most frequent symptoms were bloating and abdominal pain, and were more severe with combined fructose and lactose intolerance. During the free diet, patients reported eliminating (48%) or reducing (52%) fructose-containing foods, with a significant improvement in symptoms (abdominal pain from 79.7 ± 1.3 to 19.3 ± 1.8 mm; bloating from 83.1 ± 1.3 to 19.4 ± 1.8 mm; number of evacuations/day from 3.9 ± 0.16 to 1.1 ± 0.04; Bristol score from 5.1 ± 0.14 to 3.8 ± 0.1, P < 0.00001). During the tailored fructose-restricted diet, the consistent improvement in symptoms persisted and was similar to the improvement on free diet (abdominal pain 23.6 ± 1.9 mm; bloating 19.4 ± 1.8 mm; number of evacuations/day 1.7 ± 0.07; Bristol score 3.5 ± 0.06, P<0.00001 vs. baseline). A dose-dependent effect of fructose was observed on symptoms during the fructose breath test. CONCLUSION: In our setting, individuals with fructose intolerance show an inappropriate dietary self-management. By contrast, a tailored fructose-restricted diet improves gastrointestinal symptoms without senseless food deprivation.

Positive or negative fructose breath test results do not predict response to fructose restricted diet in children with recurrent abdominal pain: results from a prospective randomized trial.

OBJECTIVES: To perform a prospective, blinded, randomized interventional trial in patients with recurrent abdominal pain. The primary endpoint was to determine the abdominal pain intensity after 2 weeks of fructose restricted diet. Secondary endpoints were changes of pain frequency and a secondary symptom score (SSS). METHODS: 103 individuals with recurrent abdominal pain for more than 3 months were randomized. 51 patients were allocated to group A (diet) and 52 to group B (no diet). 2 weeks later the patients underwent hydrogen breath test and were assigned to the test positive or negative group to identify patients with fructose malabsorption. RESULTS: 2 weeks after intervention the pain score decreased significantly from a median 5.5 in group A to 4 and did not change significantly in group B (5.3 to 5). In group A both patients with positive and negative breath tests had a significant lower pain score (-2 and -1.75, respectively). Frequency of abdominal pain decreased in both groups but without significant difference, SSS improved only in group A from median 6 to 3.5. Positive breath test was no predicting factor, neither was abdominal pain during the test. CONCLUSIONS: Fructose restricted diet in children and adolescents with recurrent abdominal pain may be of benefit to improve both abdominal pain symptoms and other secondary symptoms. Since a negative breath test result does not exclude a positive response to fructose restriction, the hydrogen breath test does not seem to be the appropriate diagnostic mean to predict the response to the diet.

Fructose intolerance/malabsorption and recurrent abdominal pain in children.

OBJECTIVES: The purpose of the present study was to ascertain whether pediatric patients with chronic abdominal pain had concurrent fructose intolerance as determined by a standardized dose breath hydrogen test (BHT), and whether symptoms would improve with a low-fructose diet. METHODS: The fructose BHT test was administered to patients evaluated in clinic with unexplained chronic abdominal pain alone or associated with constipation, gas or bloating, and/or diarrhea. The patients were given a standard dose of 1 g/kg fructose to maximum of 25 g. Hydrogen and methane were measured at 8 time points. The test was presumed positive if breath hydrogen exceeded 20 ppm above baseline. If positive, patients were given a dietitian-prescribed low-fructose diet. RESULTS: A total of 222 patients were part of the study. Ages ranged from 2 to 19 years with a mean of 10.5. BHT for fructose was performed in all of the patients and it was positive for fructose intolerance in 121 of 222 patients (54.5%). A total of 101 of 222 (45.5%) patients had negative BHT for fructose intolerance. All BHT-positive patients had a nutrition consult with a registered dietitian and were placed on a low-fructose diet. Using a standard pain scale for children, 93 of 121 patients (76.9%) reported resolution of symptoms on a low-fructose diet (P < 0.0001). Furthermore, 55 of 101 patients (54.4%) with negative BHT for fructose reported resolution of symptoms without a low-fructose diet (P = 0.37). CONCLUSIONS: Fructose intolerance/malabsorption is common in children with recurrent/functional abdominal pain and a low-fructose diet is an effective treatment.

Dietary fructose intolerance, fructan intolerance and FODMAPs.

Dietary intolerances to fructose, fructans and FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) are common, yet poorly recognized and managed. Over the last decade, they have come to the forefront because of new knowledge on the mechanisms and treatment of these conditions. Patients with these problems often present with unexplained bloating, belching, distension, gas, abdominal pain, or diarrhea. Here, we have examined the most up-to-date research on these food-related intolerances, discussed controversies, and have provided some guidelines for the dietary management of these conditions. Breath testing for carbohydrate intolerance appears to be standardized and essential for the diagnosis and management of these conditions, especially in the Western population. While current research shows that the FODMAP diet may be effective in treating some patients with irritable bowel syndrome, additional research is needed to identify more foods items that are high in FODMAPs, and to assess the long-term efficacy and safety of dietary interventions.

The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study.

BACKGROUND AND AIM: Current treatment for irritable bowel syndrome (IBS) is suboptimal. Fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) may trigger gastrointestinal symptoms in IBS patients. Our aim was to determine whether a low FODMAP diet improves symptoms in IBS patients. METHODS: Irritable bowel syndrome patients, who had performed hydrogen/methane breath testing for fructose and lactose malabsorption and had received dietary advice regarding the low FODMAP diet, were included. The effect of low FODMAP diet was prospectively evaluated using a symptom questionnaire. Furthermore, questions about adherence and satisfaction with symptom improvement, dietary advice and diet were assessed. RESULTS: Ninety patients with a mean follow up of 15.7 months were studied. Most symptoms including abdominal pain, bloating, flatulence and diarrhoea significantly improved (p < 0.001 for all). 75.6%, 37.8% and 13.3% of patients had fructose, lactose malabsorption or small intestinal bacterial overgrowth respectively. Fructose malabsorption was significantly associated with symptom improvement (abdominal pain odds ratio (OR) 7.09 [95% confidence interval (CI) 2.01-25.0], bloating OR 8.71 (95% CI 2.76-27.5), flatulence OR 7.64 (95% CI 2.53-23.0) and diarrhoea OR 3.39 (95% CI 1.17-9.78), p < 0.029 for all). Most patients (75.6%) were adherent to the diet, which was associated with symptom improvement (abdominal pain, bloating, flatulence and diarrhoea all significantly associated with adherence, r > 0.27, p < 0.011). Most patients (72.1%) were satisfied with their symptoms. CONCLUSIONS: The low FODMAP diet shows efficacy for IBS patients. The current strategy of breath testing and dietary advice provides a good basis to understand and adhere to the diet.

[Abdominal spasms, meteorism, diarrhea: fructose intolerance, lactose intolerance or IBS?]. / Bauchschmerzen, Blähbauch, Diarrhoe: Fruktosemalabsorption, Laktoseintoleranz oder Reizdarmsyndrom?

Meteorism, abdominal spasms, diarrhea, casually obstipation, flatulence and nausea are symptoms of fructose malabsorption (FIT) and/or lactose intolerance (LIT), but are also symptoms of irritable bowel syndrome (IBS). Therefore these diseases should be considered primarily in patients with digestive complaints. For diagnosis an H(2)-breath test is used.In 1,935 patients (526 m, 1,409 f) a fructose intolerance test and in 1,739 patients (518 m,1,221 f) a lactose intolerance test was done.FIT is found more frequently than LIT (57 versus 52 % in adults (p < 0,02) and in children 90 versus 62 % (p < 0,001)) and is in polyintolerances most frequently correlated to histamine intolerance (HIT). Headache (ca. 10 %), fatigue (ca. 5 %) and dizziness (ca. 3 %) may occur after the test, irrespective whether the test was positive or negative.In more than 2/3 of patients a diet reduced in fructose or lactose may lead to improvement or remission of these metabolic disorders. IBS, which is often correlated with FIT (183/221 patients = 83 %), can be improved by relevant but also not relevant diets indicating that irritable bowel disease seems to be caused primarily by psychological disorders.

Non responsive celiac disease due to coexisting hereditary fructose intolerance.

Celiac disease is associated with several genetic disorders, but its association with hereditary fructose intolerance is rare. Hereditary fructose intolerance is a rare autosomal recessive disease of fructose metabolism presenting as vomiting after intake of fructose. An association between these two distinct genetic gastrointestinal disorders is important as treatment failure of celiac disease calls for careful evaluation for hereditary fructose intolerance. We report a patient with an association of these two disorders.

The clinical impact of carbohydrate malabsorption.

Malabsorption of carbohydrates such as fructose, lactose or sorbitol can often be detected among patients suffering from so-called non specific abdominal complaints. Sometimes the differential diagnosis may be difficult. So far successful treatment consists of dietary interventions only. Nevertheless, many questions are remaining still unanswered.

The biochemical basis of hereditary fructose intolerance.

Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecular pathological consequences of mutation of the aldolase B gene.

Fructose intolerance in IBS and utility of fructose-restricted diet.

INTRODUCTION: Whether dietary fructose intolerance causes symptoms of irritable bowel syndrome (IBS) is unclear. We examined the prevalence of fructose intolerance in IBS and long-term outcome of fructose-restricted diet. METHODS: Two hundred and nine patients with suspected IBS were retrospectively evaluated for organic illnesses. Patients with IBS (Rome II) and positive fructose breath test received instructions regarding fructose-restricted diet. One year later, their symptoms, compliance with, and effects of dietary modification on lifestyle were assessed using a structured interview. RESULTS: Eighty patients (m/f=26/54) fulfilled Rome II criteria. Of 80 patients, 31 (38%) had positive breath test. Of 31 patients, 26 (84%) participated in follow-up (mean=13 mo) evaluation. Of 26 patients, 14 (53%) were compliant with diet; mean compliance=71%. In this group, pain, belching, bloating, fullness, indigestion, and diarrhea improved (P<0.02). Of 26 patients, 12 (46%) were noncompliant, and their symptoms were unchanged, except belching. The mean impact on lifestyle, compliant versus noncompliant groups was 2.93 versus 2.57 (P>0.05). CONCLUSIONS: About one-third of patients with suspected IBS had fructose intolerance. When compliant, symptoms improved on fructose-restricted diet despite moderate impact on lifestyle; noncompliance was associated with persistent symptoms. Fructose intolerance is another jigsaw piece of the IBS puzzle that may respond to dietary modification.

Doctor, my son is so tired... about a case of hereditary fructose intolerance.

We present the case of a 17-year-old male who was diagnosed at birth with hereditary fructose intolerance (HFI). The patient complained of morning-time asthenia and post-prandial drowsiness despite a correct sleep pattern. The physical examination and biological check-up only showed severe vitamin C deficiency (<10 mol/l; normal range: 26-84). The patient's tiredness was attributed to this vitamin C deficiency, which is a frequent side-affect of the fructose-free diet. A change in diet associated with a supplementation in vitamin C was advised, with an increase in vegetable intake, principally avoiding carrots, onions, leaks and tinned sweet-corn. This case offers the opportunity for a review of this rare disease. Two kinds of fructose metabolism disorders (both autosomal recessive) are recognized: 1) essential fructosuria caused by a deficiency of fructokinase, which has no clinical consequence and requires no dietary treatment; 2) HFI, linked to three main mutations identified in aldolase B gene that may be confirmed by fructose breath test, intravenous fructose tolerance test, and genetic testing. In HFI, fructose ingestion generally induces gastro-intestinal (nausea and vomiting, abdominal pain, meteorism) and hypoglycemic symptoms. Fasting is well tolerated. If the condition remains undiagnosed, it leads to liver disease with hepatomegaly, proximal tubular dysfunction, and slow growth and weight gain. In conclusion, endocrinologists should be aware of this rare metabolic disease in order to provide careful follow-up, particularly important when the patient reaches adulthood. Moreover, hypoglycemia induced by fructose absorption, unexplained liver disease, irritable bowel syndrome or familial gout in an adult is suggestive of the diagnosis.