RESUMEN
INTRODUCTION: There is no evidence that a positive breath test is a good predictor of the success of a carbohydrate-restricted diet. Our objective was to investigate whether patients in whom lactose intolerance (LIT) or fructose intolerance (FIT) is diagnosed by validated symptom measurement respond to diet. METHODS: Patients referred for evaluation of LIT or FIT underwent hydrogen/methane breath testing (malabsorption test) and symptom measurement with the adult Carbohydrate Perception Questionnaire (aCPQ, intolerance test) before and after 50 g lactose or 25 g fructose. Patients with a positive aCPQ received instructions on specific diets and supplements. Severity of abdominal pain, bloating, diarrhoea, flatulence, and nausea were measured using a visual analogue scale (VAS) before (VAS1, mm) and after (VAS2, mm) diet. The change in VAS for individual symptoms and overall symptoms after diet is expressed as deltaVAS (mm) and as change relative to VAS1 (%). RESULTS: Forty-one patients were included (23 LIT, 8 FIT, 10 LIT+FIT). Eight patients had negative breath tests (no malabsorption). After 2 months of diet, the overall VAS and the individual symptoms decreased (p < 0.001). Overall VAS1 and the VAS1 for individual symptoms correlated significantly with the decrease in deltaVAS (mm) after diet. Nineteen patients (46%) had total recovery, and additional 13 patients (32%) had improvement of >50%. Response to diet was independent of breath test results. CONCLUSION: This uncontrolled and unblinded study suggests that patients with carbohydrate intolerance diagnosed by aCPQ benefit significantly from diet, independent of the presence of malabsorption. Controlled studies are required to confirm these results in larger patient groups.
Asunto(s)
Pruebas Respiratorias , Intolerancia a la Fructosa , Intolerancia a la Lactosa , Humanos , Intolerancia a la Lactosa/dietoterapia , Intolerancia a la Lactosa/diagnóstico , Masculino , Femenino , Adulto , Intolerancia a la Fructosa/dietoterapia , Intolerancia a la Fructosa/diagnóstico , Encuestas y Cuestionarios , Persona de Mediana Edad , Dieta Baja en Carbohidratos , Carbohidratos de la Dieta , FructosaRESUMEN
OBJECTIVES: Abdominal pain remains one of the most common referral reasons to pediatric gastroenterology. Dietary intolerances are often considered but due to various factors are hardly pursued. We observed that diet review in large number of children with abdominal pain was high in sugary foods which led to food intolerance investigation and dietary intervention. METHODS: A retrospective review was conducted of patients presenting with abdominal pain, diarrhea, or vomiting and negative GI evaluation, who underwent fructose breath testing. Patients younger than 20 years old who were seen between June 1, 2018 and March 1, 2021 were included. Statistical analysis was performed in R. RESULTS: There were 110 pediatric patients during the study period who underwent fructose breath testing, with 31% male and 69% female. The average age was 12.14 ± 4.01 years, and the average BMI was 21.21 ± 6.12. Abdominal pain was the most common presenting symptom (74.5%) followed by diarrhea and vomiting. Seventy-seven patients (70%) had a positive fructose breath test and were diagnosed with dietary intolerance to fructose. The 56 (67.5%) of those patients experienced symptoms during the breath test. Forty-three patients improved with dietary intervention. Twenty-seven on low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet and 16 on other diets. CONCLUSIONS: Based on analysis of our cohort of children with abdominal pain and high incidence of fructose intolerance as well as improvement in symptoms, following dietary changes, this condition should be considered and treated. Further investigation is needed to improve diagnostic testing but also into understanding mechanisms behind symptom presentation in this population.
Asunto(s)
Intolerancia a la Fructosa , Síndrome del Colon Irritable , Polímeros , Humanos , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Disacáridos , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/terapia , Intolerancia a la Fructosa/complicaciones , Monosacáridos , Síndrome del Colon Irritable/complicaciones , Dieta , Oligosacáridos , Dolor Abdominal/complicaciones , Diarrea/etiología , Fructosa , Vómitos/complicaciones , FermentaciónRESUMEN
Excessive intake of sugar, and particularly fructose, is closely associated with the development and progression of metabolic syndrome in humans and animal models. However, genetic disorders in fructose metabolism have very different consequences. While the deficiency of fructokinase, the first enzyme involved in fructose metabolism, is benign and somewhat desirable, missense mutations in the second enzyme, aldolase B, causes a very dramatic and sometimes lethal condition known as hereditary fructose intolerance (HFI). To date, there is no cure for HFI, and treatment is limited to avoiding fructose and sugar. Because of this, for subjects with HFI, glucose is their sole source of carbohydrates in the diet. However, clinical symptoms still occur, suggesting that either low amounts of fructose are still being consumed or, alternatively, fructose is being produced endogenously in the body. Here, we demonstrate that as a consequence of consuming high glycemic foods, the polyol pathway, a metabolic route in which fructose is produced from glucose, is activated, triggering a deleterious mechanism whereby glucose, sorbitol and alcohol induce severe liver disease and growth retardation in aldolase B knockout mice. We show that generically and pharmacologically blocking this pathway significantly improves metabolic dysfunction and thriving and increases the tolerance of aldolase B knockout mice to dietary triggers of endogenous fructose production.
Asunto(s)
Enfermedades del Sistema Digestivo , Intolerancia a la Fructosa , Hepatopatías , Humanos , Animales , Ratones , Intolerancia a la Fructosa/genética , Intolerancia a la Fructosa/diagnóstico , Fructosa/metabolismo , Fructosa-Bifosfato Aldolasa/genética , Glucosa/uso terapéutico , Ratones NoqueadosRESUMEN
We report a patient with an extremely rare, combined diagnosis of PMM2-CDG and hereditary fructose intolerance (HFI). By comparing with other patients, under-galactosylation was identified as a feature of HFI. Fructose/sorbitol/sucrose restriction was initiated right afterwards. The patient is at the mild end of the PMM2-CDG spectrum, raising the question of sorbitol's role in the pathogenesis of PMM2-CDG and whether fructose/sorbitol/sucrose restriction could benefit other PMM2-CDG patients. Additionally, epalrestat, an emerging potential PMM2-CDG therapy, may benefit HFI patients.
Asunto(s)
Trastornos Congénitos de Glicosilación , Intolerancia a la Fructosa , Fosfotransferasas (Fosfomutasas) , Humanos , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/genética , Trastornos Congénitos de Glicosilación/diagnóstico , Trastornos Congénitos de Glicosilación/genética , Fructosa/uso terapéutico , Sorbitol/uso terapéutico , Sacarosa/uso terapéuticoRESUMEN
Inflammatory bowel disease (IBD) involves two clinically defined entities, namely Crohn's disease and ulcerative colitis. Fecal calprotectin (FCAL) is used as a marker to distinguish between organic IBD and functional bowel disease in disorders of the irritable bowel syndrome (IBS) spectrum. Food components may affect digestion and cause functional abdominal disorders of the IBS spectrum. In this retrospective study, we report on FCAL testing to search for IBD in 228 patients with disorders of the IBS spectrum caused by food intolerances/malabsorption. Included were patients with fructose malabsorption (FM), histamine intolerance (HIT), lactose intolerance (LIT), and H. pylori infection. We found elevated FCAL values in 39 (17.1%) of 228 IBS patients with food intolerance/malabsorption and H. pylori infection. Within these, fourteen patients were lactose intolerant, three showed fructose malabsorption, and six had histamine intolerance. The others had combinations of the above conditions: five patients had LIT and HIT, two patients had LIT and FM, and four had LIT and H. pylori. In addition, there were individual patients with other double or triple combinations. In addition to LIT, IBD was suspected in two patients due to continuously elevated FCAL, and then found via histologic evaluation of biopsies taken during colonoscopy. One patient with elevated FCAL had sprue-like enteropathy caused by the angiotensin receptor-1 antagonist candesartan. When screening for study subjects concluded, 16 (41%) of 39 patients with initially elevated FCAL agreed to voluntarily control FCAL measurements, although symptom-free and -reduced, following the diagnosis of intolerance/malabsorption and/or H. pylori infection. After the initiation of a diet individualized to the symptomatology and eradication therapy (when H. pylori was detected), FCAL values were significantly lowered or reduced to be within the normal range.
Asunto(s)
Intolerancia a la Fructosa , Enfermedades Inflamatorias del Intestino , Síndrome del Colon Irritable , Intolerancia a la Lactosa , Síndromes de Malabsorción , Humanos , Síndrome del Colon Irritable/diagnóstico , Intolerancia Alimentaria , Complejo de Antígeno L1 de Leucocito , Estudios Retrospectivos , Histamina , Enfermedades Inflamatorias del Intestino/diagnóstico , Intolerancia a la Lactosa/diagnóstico , Intolerancia a la Fructosa/diagnóstico , Dieta , Fructosa , HecesRESUMEN
Herein, we described the case of a newborn male, from consanguineous parents, who developed, at day 11 of life, an obstructive hydrocephalus resulting from bilateral cerebellar hemorrhage without evident cause. Then, at 1 month, he developed a fulminant hepatitis with hyperammonia, hyperlactatemia and metabolic acidosis. Infectious and first line metabolic explorations were normal. Screening for congenital disorder of glycosylation (CDG) was performed using capillary electrophoresis and western blot of serum transferrin. Abnormal results were evocative of mannose-phosphate isomerase deficiency (MPI-CDG or CDG-Ib) as it can be responsible for fulminant hepatitis, digestive disease, developmental delay, and coagulopathy. However, trio whole exome sequencing revealed a pathogenic variant at the homozygous state in ALDOB, responsible for hereditary fructose intolerance (HFI), an inherited metabolic disorder with excellent prognosis under a fructose-free diet. HFI had not been previously evoked in view of the absence of diet diversification, but meticulous inquiry revealed that parents systematically added white sugar to the bottle milk of their child, unintentionally triggering potentially fatal HFI decompensations. Early genetic analysis upsetted both diagnosis and prognosis for this infant who had excellent development after fructose removal. This full-of-surprises diagnostic approach illustrates the importance of an integrative collaboration between clinicians, biochemists, and geneticists.
Asunto(s)
Trastornos Congénitos de Glicosilación , Intolerancia a la Fructosa , Necrosis Hepática Masiva , Lactante , Niño , Recién Nacido , Humanos , Masculino , Glicosilación , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/genética , Intolerancia a la Fructosa/metabolismo , Trastornos Congénitos de Glicosilación/diagnóstico , Trastornos Congénitos de Glicosilación/genética , Errores DiagnósticosRESUMEN
Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare disorder characterized by multiple small intestine ulcers. Patients with CEAS typically present with chronic anemia and gastrointestinal bleeding. Besides CEAS, SLCO2A1 mutations cause primary hypertrophic osteoarthropathy (PHO) which is considered as an extraintestinal manifestation in CEAS patients. Since CEAS and Crohn's disease are clinically indistinguishable, patients are often misdiagnosed with Crohn's disease. Herein, we describe a 4-year-old Turkish girl with CEAS due to homozygous pathogenic variant (c.656C > T) in SLCO2A1 with concomitant hereditary fructose intolerance (HFI) caused by homozygous pathogenic variant (c.1005C > G) in ALDOB. Prompt restriction of fructose, sucrose and sorbitol resulted in hepatomegaly regression and mild amelioration of patient's symptoms. Despite budesonide and azathioprine treatments, patient's protein losing enteropathy and chronic anemia did not improve. Although previous CEAS cases were reported from East Asian countries, it is likely to occur in people from other geographic areas. CEAS seems to be underdiagnosed and high index of suspicion is required for the diagnosis of this rare entity. Patients with prior diagnosis of Crohn's disease with no response to immunosuppressive treatment or anti-TNF therapy should be re-evaluated for possible CEAS diagnosis.
Asunto(s)
Anemia , Enfermedad de Crohn , Intolerancia a la Fructosa , Transportadores de Anión Orgánico , Humanos , Preescolar , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/genética , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/genética , Enfermedades Raras , Inhibidores del Factor de Necrosis Tumoral , Transportadores de Anión Orgánico/genéticaRESUMEN
Fructose intolerance (FI) is a widespread non-genetic condition in which the incomplete absorption of fructose leads to gastro-intestinal disorders. The crucial role of microbial dysbiosis on the onset of these intolerance symptoms together with their persistence under free fructose diets are driving the scientific community towards the use of probiotics as a novel therapeutic approach. In this study, we evaluated the prevalence of FI in a cohort composed of Romanian adults with Functional Grastrointestinal Disorders (FGIDs) and the effectiveness of treatment based on the probiotic formulation EQBIOTA® (Lactiplantibacillus plantarum CECT 7484 and 7485 and Pediococcus acidilactici CECT 7483). We evaluated the impact of a 30-day treatment both on FI subjects and healthy volunteers. The gastrointestinal symptoms and fecal volatile metabolome were evaluated. A statistically significant improvement of symptoms (i.e., bloating, and abdominal pain) was reported in FI patient after treatment. On the other hand, at the baseline, the content of volatile metabolites was heterogeneously distributed between the two study arms, whereas the treatment led differences to decrease. From our analysis, how some metabolomics compounds were correlated with the improvement and worsening of clinical symptoms clearly emerged. Preliminary observations suggested how the improvement of gastrointestinal symptoms could be induced by the increase of anti-inflammatory and protective substrates. A deeper investigation in a larger patient cohort subjected to a prolonged treatment would allow a more comprehensive evaluation of the probiotic treatment effects.
Asunto(s)
Intolerancia a la Fructosa , Enfermedades Gastrointestinales , Pediococcus acidilactici , Probióticos , Adulto , Fructosa , Intolerancia a la Fructosa/diagnóstico , Humanos , Metabolómica , Pediococcus , Probióticos/uso terapéuticoRESUMEN
BACKGROUND: While role of ALDOB-related gene variants for hereditary fructose intolerance is well established, contribution of gene variants for acquired fructose malabsorption (e.g. SLC2A5, GLUT5) is not well understood. METHODS: Patients referred to fructose breath test were further selected to identify those having acquired fructose malabsorption. Molecular analysis of genomic DNA included (I) exclusion of 3 main ALDOB gene variants causing hereditary fructose intolerance and (II) sequencing analysis of SLC2A5 gene comprising complete coding region, at least 20 bp of adjacent intronic regions and 700 bp of proximal promoter. RESULTS: Among 494 patients, 35 individuals with acquired fructose malabsorption were identified based on pathological fructose-breath test and normal lactose-breath test. Thirty four of them (97%) had negative tissue anti-transglutaminase and/or deamidated gliadin antibodies in their medical records. Molecular analysis of SLC2A5 gene of all 35 subjects identified 5 frequent and 5 singular gene variants mostly in noncoding regions (promoter and intron). Allele frequencies of gene variants were similar to those reported in public databases strongly implying that none of them was associated with acquired fructose malabsorption. CONCLUSIONS: Gene variants of coding exons, adjacent intronic regions and proximal promoter region of SLC2A5 gene are unlikely to contribute to genetic predisposition of acquired fructose malabsorption.
Asunto(s)
Intolerancia a la Fructosa , Pruebas Respiratorias , Exones , Fructosa , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/genética , Transportador de Glucosa de Tipo 5/genética , Humanos , Regiones Promotoras GenéticasRESUMEN
Hereditary fructose intolerance is a rare autosomal recessive metabolic disorder characterized by liver failure, renal tubulopathy, growth retardation, and occasionally death upon exposure to fructose. We present a 2-month-old male infant diagnosed with pyloric stenosis who developed disseminated intravascular coagulopathy following pyloromyotomy. Unexplained persistent coagulopathy, acute liver failure, and metabolic dysfunction led to whole-exome sequencing, which revealed compound heterozygous variants in ALDOB (p.Arg60Ter and p.Ala150Pro), diagnostic of hereditary fructose intolerance. Shortly after initiating a fructose-free diet, our patient had resolution of his coagulopathy, hepatic, and metabolic dysfunction.
Asunto(s)
Intolerancia a la Fructosa , Piloromiotomia , Dieta , Intolerancia a la Fructosa/diagnóstico , Humanos , Lactante , Hígado , MasculinoRESUMEN
Hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism of autosomal recessive inheritance caused by pathogenic variants in the ALDOB gene that lead to aldolase B deficiency in the liver, kidneys, and intestine. Patients manifest symptoms, such as ketotic hypoglycemia, vomiting, nausea, in addition to hepatomegaly and other liver and kidney dysfunctions. The treatment consists of a fructose-restricted diet, which results in a good prognosis. To analyze the distribution of ALDOB variants described in patients and to estimate the prevalence of HFI based on carrier frequency in the gnomAD database, a systematic review was conducted to assess ALDOB gene variants among patients with HFI. The prevalence of HFI was estimated from the carrier frequency of variants described in patients, as well as rare variants predicted as pathogenic by in silico tools. The p.(Ala150Pro) and p.(Ala175Asp) variants are the most frequent and are distributed worldwide. However, these variants have particular distribution patterns in Europe. The analysis of the prevalence of HFI showed that the inclusion of rare alleles predicted as pathogenic is a more informative approach for populations with few patients. The data show that HFI has a wide distribution and an estimated prevalence of ~1:10,000.
Asunto(s)
Intolerancia a la Fructosa , Alelos , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/epidemiología , Intolerancia a la Fructosa/genética , Fructosa-Bifosfato Aldolasa/genética , Humanos , Hígado/patología , MutaciónRESUMEN
BACKGROUND: Symptoms following fructose ingestion, or fructose intolerance, are common in patients with functional gastrointestinal disorders (FGID) and are generally attributed to intestinal malabsorption. The relationships between absorption, symptoms, and intestinal gas production following fructose ingestion were studied in patients with FGID. METHODS: Thirty FGID patients ingested a single dose of fructose 35 g or water in a randomized, double-blind, crossover study. Blood and breath gas samples were collected, and gastrointestinal symptoms rated. Plasma fructose metabolites and short-chain fatty acids were quantified by targeted liquid chromatography-tandem mass spectrometry. Patients were classified as fructose intolerant or tolerant based on symptoms following fructose ingestion. KEY RESULTS: The median (IQR) areas under the curve of fructose plasma concentrations within the first 2 h (AUC0-2 h ) after fructose ingestion were similar for patients with and without fructose intolerance (578 (70) µM·h vs. 564 (240) µM·h, respectively, p = 0.39), as well as for the main fructose metabolites. There were no statistically significant correlations between the AUC0-2 h of fructose or its metabolites concentrations and the AUCs of symptoms, breath hydrogen, and breath methane. However, the AUCs of symptoms correlated significantly and positively with the AUC0-2 h of hydrogen and methane breath concentrations (r = 0.73, r = 0.62, respectively), and the AUCs of hydrogen and methane concentrations were greater in the fructose-intolerant than in the fructose-tolerant patients after fructose ingestion (p ≤ 0.02). CONCLUSIONS & INFERENCES: Fructose intolerance in FGID is not related to post-ingestion plasma concentrations of fructose and its metabolites. Factors other than malabsorption, such as altered gut microbiota or sensory function, may be important mechanisms.
Asunto(s)
Intolerancia a la Fructosa/complicaciones , Enfermedades Gastrointestinales/complicaciones , Síndromes de Malabsorción/complicaciones , Adulto , Pruebas Respiratorias , Estudios Cruzados , Método Doble Ciego , Ácidos Grasos Volátiles/sangre , Femenino , Fructosa/administración & dosificación , Intolerancia a la Fructosa/sangre , Intolerancia a la Fructosa/diagnóstico , Enfermedades Gastrointestinales/sangre , Humanos , Síndromes de Malabsorción/sangre , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by a mutation in the aldolase B gene. HFI patients exhibit nausea, vomiting, abdominal pain, hypoglycemia, and elevated liver enzymes after dietary fructose exposure. Chronic exposure might lead to failure to thrive, liver failure, renal failure, and, eventually, death. HFI usually manifests in infants when they are being weaned off of breastmilk. Because HFI has an excellent prognosis when patients maintain a strict restrictive diet, some patients remain undiagnosed due to the voluntary avoidance of sweet foods. In the past, HFI was diagnosed using a fructose tolerance test, liver enzyme assays or intestinal biopsy specimens. Currently, HFI is diagnosed through the analysis of aldolase B mutations. Here, HFI was diagnosed in a 41-year-old woman who complained of sweating, nausea, and vomiting after consuming sweets. She had a compound heterozygous mutation in the aldolase B gene; gene analysis revealed pathogenic nonsense (c.178C>T, p.Arg60Ter) and frameshift (c.360_363delCAAA, p.Asn120LysfsTer32) variants. This is the first report of a Korean HFI patient diagnosed in adulthood.
Asunto(s)
Intolerancia a la Fructosa , Adulto , Femenino , Fructosa , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/genética , Fructosa-Bifosfato Aldolasa/genética , Humanos , Hígado , MutaciónRESUMEN
ABSTRACT: Fructose is a highly abundant carbohydrate in western diet and may induce bowel symptoms in children as in adults. The main objective of this study is to describe the frequency of fructose malabsorption (FM) in symptomatic patients 18 years or younger undergoing fructose breath test in a single tertiary center between 2013 and 2018, and to evaluate whether certain symptoms are related to positivity of the test. Out of 273 tests 183 (67%) were compatible with FM. The most frequent pretest symptom in the overall study population was bloating (83%), followed by abdominal pain (73%). Patients with positive test were younger than those with a negative test (median 5 vs 8 years, Pâ<â0.001). In multivariate analysis, which included age, sex, and symptoms (diarrhea, abdominal pain, bloating, nausea), only age <6âyears (odds ratio 2.93, 95% confidence interval 1.64-5.23) and absence of nausea (odds ratioâ=â3.32, 95% confidence interval 1.56-7.05) were associated with FM.
Asunto(s)
Intolerancia a la Fructosa , Síndromes de Malabsorción , Dolor Abdominal , Adulto , Pruebas Respiratorias , Niño , Chile/epidemiología , Fructosa/efectos adversos , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/epidemiología , Humanos , Síndromes de Malabsorción/diagnóstico , Síndromes de Malabsorción/epidemiología , Síndromes de Malabsorción/etiología , Centros de Atención TerciariaAsunto(s)
Dietoterapia/métodos , Intolerancia a la Fructosa , Fructosa-Bifosfato Aldolasa/genética , Hepatomegalia , Sacarosa/efectos adversos , Evaluación de Síntomas/métodos , Preescolar , Diagnóstico Tardío/prevención & control , Diagnóstico Diferencial , Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/fisiopatología , Intolerancia a la Fructosa/terapia , Frutas/efectos adversos , Hepatomegalia/diagnóstico , Hepatomegalia/etiología , Humanos , Recién Nacido , Pruebas de Función Hepática/métodos , Masculino , Mutación , Bebidas Azucaradas/efectos adversos , Vómitos/diagnóstico , Vómitos/etiologíaRESUMEN
Carbohydrate malabsorption and subsequent gastrointestinal symptoms are a common clinical problem in pediatrics. Hydrogen (H2) and methane (CH4) breath tests are a cheap and non-invasive procedure for diagnosing fructose and lactose malabsorption (FM/LM) but test accuracy and reliability as well as the impact of non-hydrogen producers (NHP) is unclear. CH4 breath tests (MBT), blood sugar tests (BST) and clinical symptoms were compared with H2 breath tests (HBT) for FM/LM. 187/82 tests were performed in children (2 to 18 years) with unclear chronic/recurrent abdominal pain and suspected FM/LM. In FM and LM, we found a significant correlation between HBT and MBT/BST. In LM, MBT differentiated most of the patients correctly and BST might be used as an exclusion test. However, additional MBT and BST had no diagnostic advantage in FM. NHP still remain a group of patients, which cannot be identified using the recommended CH4 cut-off values in FM or LM. Reported symptoms during breath tests are not a reliable method to diagnose FM/LM. Overall a combined test approach might help in diagnosing children with suspected carbohydrate malabsorption.
Asunto(s)
Intolerancia a la Fructosa/diagnóstico , Hidrógeno/análisis , Intolerancia a la Lactosa/diagnóstico , Metano/análisis , Adolescente , Glucemia , Pruebas Respiratorias , Niño , Preescolar , Femenino , Intolerancia a la Fructosa/sangre , Humanos , Intolerancia a la Lactosa/sangre , Masculino , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
INTRODUCTION: Patients with functional gastrointestinal disorders (FGIDs) are classified based on their gastrointestinal (GI) symptoms, without considering their frequent extra-GI symptoms. This study defined subgroups of patients using both GI and extra-GI symptoms and examined underlying mechanisms with fructose and lactose breath tests. METHODS: Latent class analysis defined distinct clusters of patients with FGID based on their long-term GI and extra-GI symptoms. Sensory and breath gas responses after fructose and lactose ingestion were compared across symptom clusters to investigate differences in sensory function and fermentation by intestinal microbiota. RESULTS: Six symptom clusters were identified in 2,083 patients with FGID. Clusters were characterized mainly by GI fermentation-type (cluster 1), allergy-like (cluster 2), intense pain-accentuated GI symptoms (cluster 3), central nervous system (cluster 4), musculoskeletal (cluster 5), and generalized extra-GI (cluster 6) symptoms. In the 68% of patients with complete breath tests, the areas under the curve of GI and central nervous system symptoms after fructose and lactose ingestion differed across the clusters (P < 0.001). The clusters with extensive long-term extra-GI symptoms had greater symptoms after the sugars and were predominantly women, with family or childhood allergy histories. Importantly, the areas under the curves of hydrogen and methane breath concentrations were similar (P > 0.05) across all symptom clusters. Rome III criteria did not distinguish between the symptom clusters. DISCUSSION: Patients with FGID fall into clusters defined extensively by extra-GI symptoms. Greater extra-GI symptoms are associated with evidence of generalized sensory hypersensitivity to sugar ingestion, unrelated to intestinal gas production. Possible underlying mechanisms include metabolites originating from the intestinal microbiota and somatization.
Asunto(s)
Intolerancia a la Fructosa/diagnóstico , Microbioma Gastrointestinal/fisiología , Intolerancia a la Lactosa/diagnóstico , Trastornos Somatomorfos/diagnóstico , Adulto , Pruebas Respiratorias/métodos , Diagnóstico Diferencial , Femenino , Fermentación , Fructosa/administración & dosificación , Fructosa/análisis , Fructosa/metabolismo , Intolerancia a la Fructosa/psicología , Humanos , Lactosa/administración & dosificación , Lactosa/análisis , Lactosa/metabolismo , Intolerancia a la Lactosa/psicología , Masculino , Persona de Mediana Edad , Trastornos Somatomorfos/psicología , Adulto JovenRESUMEN
Establishing the diagnosis of hereditary fructose intolerance (HFI) remains difficult despite the availability of specific molecular genetic testing of the ALDOB gene. This is attributable, at least in part, to the lack of a specific and practical biomarker. We report the incidental diagnosis of HFI as a consequence of nontargeted genetic testing ordered for alternative indications in 5 patients, including 3 children and 2 adults. Two of the children were diagnosed with HFI after extensive evaluations that ultimately involved clinical or research exome sequencing. The third child was diagnosed with HFI during subsequent genetic testing of at-risk family members. Both adults learned to avoid fructose and remained asymptomatic of HFI before diagnosis. One was diagnosed with HFI during preconception, nontargeted expanded carrier screening. For the other, concern for HFI was initially raised by indeterminate direct-to-consumer genetic testing results. None of these patients presented with infantile acute liver failure or other acute decompensation. Our findings suggest that the emphasis of classic teaching on infantile liver failure after first exposure to fructose may be inadvertently increasing the likelihood of missing cases of HFI characterized by other manifestations. HFI is likely underdiagnosed and should be considered for patients with nonspecific findings as well as for individuals with significant aversion to sweets.
Asunto(s)
Intolerancia a la Fructosa/diagnóstico , Adulto , Anciano , Enfermedades Asintomáticas , Niño , Preescolar , Discapacidades del Desarrollo/genética , Pruebas Dirigidas al Consumidor , Enanismo/genética , Insuficiencia de Crecimiento/genética , Femenino , Preferencias Alimentarias , Intolerancia a la Fructosa/genética , Fructosa-Bifosfato Aldolasa/genética , Frutas/efectos adversos , Pruebas Genéticas , Humanos , Hallazgos Incidentales , Infertilidad Femenina , Masculino , Atención Preconceptiva , Verduras/efectos adversos , Secuenciación del ExomaRESUMEN
Children with chronic idiopathic constipation (CIC) often end up at the surgeon when medical treatments have failed. This opinion piece discusses a recently described pattern of CIC called 'Rapid transit constipation (RTC)' first identified in 2011 as part of surgical workup. RTC was identified using a nuclear medicine gastrointestinal transit study (NMGIT or nuclear transit study) to determine the site of slowing within the bowel and to inform surgical treatment. Unexpectedly, we found that RTC occured in 29% of 1000 transit studies in a retrospective audit. Irritable bowel syndrome (IBS) occurs in 7-21% of the population, with a higher prevalence in young children and with constipation type dominating in the young. While 60% improve with time, 40% continue with symptoms. First-line therapy for IBS in adults is a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols which reduces symptoms in > 70% of patients. In children with functional gastrointestinal disorders, fructose intolerance occurs in 35-55%. Reducing fructose produced significant improvement in 77-82% of intolerant patients. In children with RTC and a positive breath test upon fructose challenge, we found that exclusion of fructose significantly improved constipation, abdominal pain, stool consistency and decreased laxative use. We hypothesise that positive breath tests and improvement of pain and bowel frequency with sugar exclusion diets in RTC suggest these children have IBS-C. These observations raise the possibility that many children with CIC could be treated by reducing fructose early in their diet and this might prevent the development of IBS in later life.