Iron absorption and iron deficiency in infants and children with gastrointestinal diseases.

Iron status, iron absorption, and intestinal blood loss were studied in 199 children undergoing diagnostic evaluation for suspected malabsorption. Evaluation of iron status included hematological indices, serum ferritin, and transferrin saturation. Iron absorption was assessed by the increment of serum iron after an oral iron load. Iron deficiency was common among patients affected by malabsorptive states, such as celiac disease (84%), cow's milk intolerance (76%), Crohn's disease (72%), and giardiasis (64%), whereas it was less common among patients with postinfectious enteritis (41%) and chronic nonspecific diarrhea (11%). Intestinal blood loss was seen only in patients with Crohn's disease and cow's milk intolerance, irrespective of iron nutritional status. On the other hand, iron malabsorption was very common, affecting 85-95% of the iron-deficient patients in all diagnostic groups, except in chronic nonspecific diarrhea. Iron malabsorption was less common among patients with adequate iron nutritional status than in those with iron deficiency. Iron malabsorption appears to play a major role in the pathogenesis of iron deficiency in patients with malabsorption. The iron absorption test shows greater sensitivity as a screening test for upper intestinal malabsorption than the D-xylose absorption test.     

Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease

In the absence of dietary insufficiency, iron deficiency is usually caused by chronic blood loss or intestinal malabsorption. Celiac disease is one of the most common causes of intestinal malabsorption during childhood, and its association with insulin-dependent diabetes mellitus has been previously reported. Here the authors describe an otherwise asymptomatic diabetic adolescent boy with iron deficiency anemia that was not responsive to oral iron therapy. A diagnosis of celiac disease was made based on both anti-endomysial antibody titers and small intestinal biopsy. Institution of a gluten-free diet resulted in correction of the anemia. These observations emphasize the importance of considering a diagnosis of celiac disease in patients with nonresponsive iron deficiency anemia, particularly in the setting of insulin-dependent diabetes mellitus.     

Iron malabsorption in giardiasis

Among 10 children with giardiasis, eight had iron deficiency; iron deficiency anemia was the main complaint in three. Evaluation of iron absorption by the oral iron load test demonstrated a subnormal response (i.e., increase in serum iron levels of less than 100 micrograms/dl) in all eight patients with iron deficiency. In contrast, in two iron-sufficient patients with giardiasis the response to an oral iron load was normal. Xylose absorption was abnormal in five of the 10 patients. After metronidazole dosing, iron absorption became normal in seven patients but remained abnormal in one patient, who also had IgA deficiency. Xylose absorption became normal in all five patients who underwent a second test, but remained abnormal in the patient with IgA deficiency. Concomitant morphologic-studies of jejunal biopsy material from these patients revealed moderate changes in the intestinal mucosa of two patients. We conclude that malabsorption of iron is a complication of giardiasis.     

Giardiasis: haematological status and the absorption of vitamin B12 and folic acid

The haematological status, as well as the fractional absorptions of folic acid (FAFol) and vitamin B12 (FAB12) were studied in 29 children aged 0.7-13.5 years (mean 3.3 years) with chronic diarrhoea due to giardiasis. Small intestinal biopsies revealed mucosal damage in 20 children; the biopsies of the remaining nine children were normal. At the initial investigation the FAFol and FAB12 values were below normal in approximately one-sixth and one-third of patients, respectively. Bacterial overgrowth of the small intestinal tract did not seem to play a role in FAB12 malabsorption. About one-fifth of patients had mild anaemia. None of the patients showed FAB12 insufficiency and only one patient suffered from folate depletion. At follow-up, FAFol, FAB12, haemoglobin and Erc-folate concentrations increased significantly while P-B12 and P-folate remained unchanged. Iron status, as well as dietary intake of iron, appeared insufficient prior to, as well as after treatment. Serum iron, transferrin saturation and haemoglobin concentrations were lower in patients who had acquired the disease abroad or suffered from persistent diarrhoea.     

Ferrokinetics in the syndrome of familial hypoferremic microcytic anemia with iron malabsorption.

PURPOSE: In 1981, Buchanan and Sheehan described a previously unreported syndrome in three siblings who had iron malabsorption, hypoferremia, and microcytic anemia that did not respond to oral iron and responded only partly to parenteral iron dextran. Ferrokinetic studies were not done in these or subsequently reported patients with this syndrome. It has been postulated that this syndrome of abnormal iron metabolism is analogous to that observed in the mk/mk mouse, which has similar hematologic findings but also has abnormal ferrokinetics. Ferrokinetic studies were performed in one patient to determine whether the abnormality of iron metabolism in the human syndrome is analogous to the mk/mk mouse. PATIENTS AND METHODS: Two sisters with severe microcytic anemia and iron malabsorption who have had only partial response to parenteral iron have been followed up for 15 years. Ferrokinetic studies with 59Fe were performed in one sister. RESULTS: Ferrokinetic studies with radio iron were characteristic of iron deficient erythropoiesis (rapid 59Fe T1/2; rapid, complete incorporation of 59Fe into erythrocyte hemoglobin). These ferrokinetics differ from those of the mk/mk mouse, which has a missense mutation in Nramp2, a putative iron transporter protein. In these children, once iron enters the plasma its subsequent metabolism (including binding to transferrin), transfer into erythroid bone marrow cells, and subsequent incorporation into erythrocyte hemoglobin are all normal. The defect in these patients appears to be an undefined, novel abnormality that governs mobilization of iron into the plasma from both the intestinal mucosal and reticuloendothelial cells. Despite lifelong severe hypoferremia, the growth, development and intellectual performance of these children, who are teen-agers, are normal.     

Serum IgA and IgG gliadin antibodies and small intestinal mucosal damage in children

Serum immunoglobulin (Ig) A and IgG gliadin antibodies were determined with a simple, rapid, and inexpensive method--diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA)--and the results were related to small intestinal mucosal morphology in 234 children suspected of having malabsorption. Fifty-six of 58 children with flat intestinal mucosa had increased IgA and/or IgG gliadin antibody levels (sensitivity 97%). Fifty-four of the 58 children had celiac disease (CD) (n = 25) or probable CD (n = 29). Four children with flat mucosa had cow's milk protein and/or soy protein intolerance and three of these had increased gliadin antibody levels. Seventeen percent of 132 children with normal intestinal mucosa had increased IgA and/or IgG gliadin antibody levels. IgA and IgG gliadin antibody levels decreased significantly in the celiac children on a gluten-free diet and increased significantly after gluten challenge. Determination of serum IgA and IgG gliadin antibodies by means of DIG-ELISA is a sensitive test for small intestinal mucosal damage in children. When malabsorption is suspected, we suggest that this assay be used to select children for a small intestinal biopsy. It is also very useful for the follow-up of adherence to a gluten-free diet and to determine the effect of gluten challenge in celiac children.     

Octreotide in the treatment of small intestinal dysfunction after a model of jejunoileal autotransplantation in the pig

Enteric denervation and ischemic injury contribute to dysmotility and malabsorption following intestinal transplantation. We hypothesized that, by prolonging bowel transit and by ameliorating dysmotility, octreotide (OT) may improve cholesterol and bile acid absorption after jejunoileal autotransplantation. Seventeen pigs with fixed food intake underwent either jejunal transection (n=6), or jejunoileal autotransplantation, which includes extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia (n=11). Five randomly chosen autotransplanted animals received intramuscular long-acting OT (10 mg) once a month. After 8 weeks, weight gain, intestinal transit time, fecal excretion of bile acids and cholesterol, and fractional cholesterol absorption were determined. Jejunal and ileal specimens were collected for histochemical analyses. Plasma cholestenol and campesterol, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. Following jejunoileal autotransplantation, octreotide treatment significantly increased the median intestinal transit time from 22.8 to 24.8 h and the median body weight gain from 166 to 187%. Jejunoileal autotransplantation significantly increased fecal bile acid excretion, plasma cholestenol, and bacterially modified fecal neutral sterols, and decreased absorption of cholesterol, plasma campesterol, and biliary cholesterol secretion. These changes were not significantly modified by OT treatment. Bowel wall and mucosal structure, mucosal proliferation, and weight or microvilli showed no statistically significant differences between autotransplanted animals with or without OT treatment. Findings of the present study suggest that octreotide prolongs intestinal transit time and improves weight gain after jejunoileal autotransplantation, but has no effect on malabsorption of cholesterol and bile acids.     

Morphometric and immunohistochemical study of jejunal biopsies from chilren with intestinal soy allergy

A morphometric and immunohistochemical restudy was made of jejunal biopsy specimens from 5 patients with soy allergy and the results obtained were compared to those from specimens taken before soy feeding and to those at a later time. All the patients had had previous cow's milk allergy with malabsorption. Gastrointestinal symptoms presented within two weeks of starting the soy based formula but in two patients the symptoms were mild and these patients were able to continue soy feeding. Jejunal biopsy specimens taken within 3 days from the reaction to soy showed villous atrophy associated with crypt hyperplasia and an increased cell renewal rate. Also, these specimens showed an inflammatory reaction in the lamina propria and in the epithelium, and the numbers of IgA- and IgM-containing cells were increased. Later, when the soy proteins were eliminated, the morphology of the jejunum improved and the cell numbers were reduced to normal.The intestinal damage and the local immune reaction caused by soy proteins are similar to those seen in cow's milk allergy with malabsorption. The immunological mechanisms operating in these diseases are thought to be the cause of these changes.     

Sclerosis of the intestinal tract with severe malabsorption

The clinical findings and pathological changes in a 14 year old boy who died from severe malabsorption are presented. Early signs of the illness were attacks of abdominal pain, diarrhoea, and intermittent periods of constipation. Later, severe malabsorption together with chronic ileus were apparent but no organic obstruction was found at several laparotomies. X-ray examination revealed extremly distended intestinal loops and a very slow transit time of barium. Malnutrition could not be improved by dietary, medical, or surgical therapy. Microscopic examination of the tissues obtained at autopsy showed changes in the small vessels of the lungs, heart, kidneys, and intestine. Increased fibrous tissue combined with atrophy of the muscular coat was observed in the wall of the entire intestine. Although cutaneous changes of scleroderma were not evident the deposition of collagenous material and the vascular changes seem typical of systemic sclerosis.     

JEJUNAL MUCOSA IN INFANTILE MALNUTRITION

Twenty-six infants with malnutrition and seven controls were studied by routine haematological tests, serum protein levels, glucose tolerance and D-Xylose absorption tests, jejunal biopsies and intestinal disaccharidase, assays. In conclusion, it can be said that in malnutrition the jejunal mucosa shows some mild or non-specific histologic changes compatible with malabsorption, which may be reversible. No correlation could be shown between these changes and absorption tests. Malnutrition may also result in secondary intestinal disaccharidase deficiencies which improve with correction of the nutritional state. These secondary enzyme deficiencies may be responsible for some of the diarrhoeas seen in marasmic children. No direct correlation between anaemia, iron-deficiency, folic acid levels, protein deficiency and intestinal mucosal changes could be established in this study.     

Enteropathy in Niemann-Pick disease

Three consecutive cases of Niemann-Pick disease with predominant enteropathy were seen. The diagnosis was confirmed by the demonstration of typical foamy cells in the bone marrow, small intestinal mucosa, and liver. The enteropathy was apparent in steatorrhoea, xylose malabsorption, protein loss etc. The hypothesis of foamy cell infiltration of the lamina propria of the small intestinal mucosa as a cause of malabsorption is proposed.     

Zinc and copper in hair and plasma of children with chronic diarrhea

Zinc and copper status was evaluated in nineteen children with chronic diarrhea. An intestinal biopsy suggested that eight of these patients had celiac disease and eleven suffered chronic diarrhea without malabsorption and had normal villi or minimal changes. They were studied for malabsorption and compared with two control groups consisting of nineteen healthy and eleven malnourished children. Plasma zinc was depressed in the celiac disease group when compared with the normal children, but was similar to that of the malnourished children. Hair zinc was also depressed for the chronic diarrhea groups (23.2 +/- 15.2 and 34.4 +/- 21.9 micrograms/g for those with or without malabsorption respectively, vs. 97.9 +/- 15.2 for the healthy group). Plasma and hair copper values were diminished in both groups with chronic diarrhea. A significant correlation was found between plasma carotene levels after oral carotene overload, and both plasma zinc and hair copper values (r = 0.62, p less than 0.01 and r = 0.56, p less than 0.05, respectively). There was also a significant correlation between plasma zinc and plasma protein (r = 0.54, p less than 0.05). Hair determinations seem to be more sensitive than plasma values to changes in zinc or copper status in chronic diarrhea. Chronic diarrhea in children is associated with lower levels of zinc and copper, especially when accompanied by malabsorption.     

Inherited selective intestinal cobalamin malabsorption and cobalamin deficiency in dogs

Inherited selective intestinal malabsorption of cobalamin (Cbl) was observed in a family of giant schnauzer dogs. Family studies and breeding experiments demonstrated simple autosomal recessive inheritance of this disease. Affected puppies exhibited chronic inappetence and failure to thrive beginning between 6 and 12 wk of age. Neutropenia with hypersegmentation, anemia with anisocytosis and poikilocytosis, and megaloblastic changes of the bone marrow were present. Serum Cbl concentrations were low, and methylmalonic aciduria and homocysteinemia were present. Parenteral, but not oral, cyanocobalamin administration rapidly eliminated all signs of Cbl deficiency except for low serum Cbl concentrations. Cbl malabsorption in affected dogs was documented by oral administration of [57Co]cyanocobalamin with or without simultaneous oral administration of intrinsic factor or normal dog gastric juice. Quantitation and function studies of intrinsic factor and transcobalamin-II from affected dogs revealed no abnormality. Other gastrointestinal functions and ileal morphology were normal, indicating a selective defect of Cbl absorption at the level of the ileal enterocyte. Immunoelectron microscopy of ileal biopsies showed that the receptor for intrinsic factor-Cbl complex was absent from the apical brush border microvillus pits of affected dogs. This canine disorder resembles inherited selective intestinal Cbl malabsorption (Imerslund-Gr?sbeck syndrome) in humans, and is a spontaneously occurring animal model of early onset Cbl deficiency.     

Serological levels of zinc, copper and iron elements among Giardia lamblia infected children in Turkey

BACKGROUND: Giardiasis, an intestinal protozoan infection caused by Giardia lamblia, is common in Turkey, especially among children aged between 2- and 14-years-old. Effects of giardiasis on serological levels of zinc, copper and iron elements were assessed in this study. METHODS: A total of 45 children, aged between 2- and 14-years-old, who were admitted to the Pediatrics Department of Celal Bayar University Medical School with gastrointestinal complaints and diagnosed as having giardiasis by stool examinations in the Parasitology Department, were enrolled as the study group (SG). The control group (CG) consisted of 45 age-matched healthy children. Serological levels of zinc, copper and iron were measured by atomic absorption spectrophotometer in all samples. RESULTS: As a result of the study, serum zinc levels were 67.43 +/- 17.72 microg/dL and 145.20 +/- 9.13 microg/dL, copper levels were 198.45 +/- 39.14 microg/dL and 150 +/- 21.14 microg/dL and iron levels were 87.98 +/- 18.31 microg/dL and 160.45 +/- 45.40 microg/dL, in SG and CG, respectively. When compared separately as SG and CG, there was a statistically significant difference between the serological levels of all these elements. CONCLUSION: These results revealed that giardiasis increased the serological levels of copper, like other infectious agents. However, zinc and iron levels decreased during giardiasis due to malabsorption.     

Zinc and Copper in Hair and Plasma of Children with Chronic Diarrhea

ABSTRACT. Zinc and copper status was evaluated in nineteen children with chronic diarrhea. An intestinal biopsy suggested that eight of these patients had celiac disease and eleven suffered chronic diarrhea without malabsorption and had normal villi or minimal changes. They were studied for malabsorption and compared with two control groups consisting of nineteen healthy and eleven malnourished children. Plasma zinc was depressed in the celiac disease group when compared with the normal children, but was similar to that of the malnourished children. Hair zinc was also depressed for the chronic diarrhea groups (23.2± 15.2 and 34.4±21.9 μg/g for those with or without malabsorption respectively, vs. 97.9± 15.2 for the healthy group). Plasma and hair copper values were diminished in both groups with chronic diarrhea. A significant correlation was found between plasma carotene levels after oral carotene overload, and both plasma zinc and hair copper values ( r =0.62, P <0.01 and r =0.56, p <0.05, respectively). There was also a significant correlation between plasma zinc and plasma protein ( r =0.54, p <0.05). Hair determinations seem to be more sensitive than plasma values to changes in zinc or copper status in chronic diarrhea. Chronic diarrhea in children is associated with lower levels of zinc and copper, especially when accompanied by malabsorption.     

Intestinal fructose malabsorption is associated with increased lactulose fermentation in the intestinal lumen

Objective

To study fructose malabsorption in children and adolescents with abdominal pain associated with functional gastrointestinal disorders. As an additional objective, the association between intestinal fructose malabsorption and food intake, including the estimated fructose consumption, weight, height, and lactulose fermentability were also studied.

The Impact of Gluten on Haematological Status, Dietary Intakes of Haemopoietic Nutrients and Vitamin B12 and Folic Acid Absorption in Children with Coeliac Disease

ABSTRACT. The haematological status, as well as the fractional absorptions of folic acid-and of vitamin B₁₂ (FAFol and FAB₁₂) were studied longitudinally in 20 coeliac children aged 1.2-16.6 yr (mean 7.5 yr) during periods of gluten-free and gluten containing diets. The absorption methods were specially adapted to use in children, and age-related reference limits were established. Also, dietary intakes of iron, folate and B₁₂ were registered. The haemoglobin concentrations did not show any significant differences in relation to shifts in diet. A few had mild anaemia while the haemoglobin concentrations in the other patients remained within normal range. The iron status, as judged from mean corpuscular volume (MCV), serum (S)-iron, S-transferrin and saturation %, appeared to be generally insufficient. However, the only significant change related to shifts in diet was an increase of S-iron during the first period of gluten-free diet. Dietary intakes of iron proved to be insufficient, regardless of the type of diet. Plasma (P)-B₁₂ concentrations demonstrated a wide range of values above the lower normal limit, whereas the level in a single patient was within the “intermediate range” of B₁₂ insufficiency (150-200 pmol/l). The folate status (erythrocyte-folate) showed significant variations related to dietary changes. However, few patients were folate depleted. FAFol and FAB₁₂ demonstrated rapidly occurring, and significant decreases and increases in relation to gluten challenge and gluten-free diet, respectively. Bacterial overgrowth of the small intestinal tract was not found to be a plausible cause of the B₁₂ malabsorption in the case of 5 patients observed. In conclusion, it is recommended that the dietary management of coeliac patients with regard to haemopoietic nutrients focus on an appropriate iron intake. While a few patients failing to keep a strict gluten-free diet risk folate depletion due to malabsorption and to inadequate intake, these patients are, on the other hand, unlikely to develop vitamin B₁₂ deficiency.     

THE MECHANISM OF DIARRHOEA IN CONGENITAL DISACCHARIDE MALABSORPTION

Intestinal malabsorption of lactose and sucrose, and the effect of these disaccharides on the movements of water and electrolytes were studied in two siblings with congenital lactose malabsorption (CLM) and one infant with congenital sucroseisomaltose malabsorption (CSIM), using the intestinal intubation technique. Sucrose in the CLM-patients and lactose in the CSIM-patient were absorbed already in the proximal part of the small intestine, whereas hardly any lactose in CLM and sucrose in CSIM disappeared from the small intestinal lumen. The unabsorbed disaccharides caused considerable movement of water and electrolytes into the intestinal lumen test fluid being diluted to 1 1/2–2 1/2 times in the duodenum and proximal jejunum. The contents of the small intestine were throughout isoosmotic with extracellular fluid and the unabsorbed disaccharides represented 25–30% of the osmotic activity. In the colon, the unabsorbed disaccharides disappeared in varying degree, they were split into monosaccharides and converted to lactate. Water, Na⁺ and Cl^- were absorbed in the colon even in relative excess to the disappearance of the disaccharide and its splitting products, and in all cases the faecal volume was smaller than the volume of the test fluid. In a CLM-patient a 3-week period on lactose-containing diet had no effect on the phenomena demonstrated in the small intestine, but disappearance of lactose and formation of lactate was greater in the colon, and amount of water less in the stools than before. It is suggested that the retention of water in the intestinal lumen through the osmotic activity of the unabsorbed disaccharide, together with the organism's tendency to Na⁺-equilibrium between the luminal and extracellular fluid is the most important mechanism of diarrhoea in disaccharide malabsorption.     

The status of lactose absorption in Hong Kong Chinese children

Lactose malabsorption was investigated in 169 Chinese children aged between two and 16 years using the breath hydrogen test. The challenge was either lactose solution (1 g/kg) or cow's milk (10 ml/kg). Overall, 68% of the children showed a significant increase in breath hydrogen following the lactose challenge while only 17% showed an increase after the cow's milk challenge and 13% after both challenges. The number of malabsorbers increased significantly (p less than 0.001) with age and no associated gastrointestinal symptoms or signs were found in any of the children following the challenges, suggesting a gradual and partial loss of intestinal lactase activity. We conclude that the prevalence of lactose malabsorption in Hong Kong children is very high using the standard lactose tolerance test but when a more realistic amount of lactose and a natural medium such as a glass of milk is used as the challenge, the number of malabsorbers becomes small and clinically insignificant.