Fructose-induced hyperuricemia: observations in normal children and in patients with hereditary fructose intolerance and galactosemia.

After the infusion of fructose, 0.25 g/kg body wt, the mean peak plasma uric acid level was 5.4 +/- 0.7 (SEM) mg/100 ml in six normal children and was not significantly increased compared with that of the mean basal value of 4.1 +/- 0.5 mg/100 ml. The mean blood inorganic phosphate (Pi) levels were significantly less than the mean fasting value after fructose. Blood glucose, lactic acid, and fructose levels were significantly increased after fructose, but serum magnesium levels did not change. In two patients with hereditary fructose intolerance (HFI) the peak blood uric acid levels were 12.1 and 7.6 mg/100 ml, respectively, after fructose. In both patients the blood glucose concentrations decreased 69 and 26 mg/100 ml below the fasting levels after fructose. The serum Pi level decreased 2.3 and 1.2 mg/100 ml below fasting values, decrements greater than the mean decrement in serum Pi of 0.8 +/- 0.2 mg/100 ml which occurred in six normal children. The mean uric acid excretion, expressed as milligrams per mg urinary creatinine, was 0.6 +/- 0.1 (SEM) before fructose in the normal children and increased significantly to 1.0 +/- mg/mg creatinine after fructose. In two patients with HFI the uric acid excretion increased four- to fivefold after fructose administration; the increased uric acid excretion in HFI exceeded that of normal children. In three patients with galactosemia, increases in blood uric acid levels after galactose ingestion were similar to those in normal children after fructose, but less than those in patients with HFI after fructose. The serum Pi levels decreased less in galactosemic patients after galactose administration than in patients with HFI after fructose infusion. These studies support the hypothesis that fructose-induced hyperuricemia results from degradation of adenosine monophosphate. This effect appears to be specific for fructose. The lack of hyperruricemia in galactosemia patients after galactose ingestion may be explained by the observation that galactose is phosphorylated more slowly than fructose.     

Increased concentrations of HbAlab in hereditary fructose intolerance and galactosemia

In patients with diabetes mellitus nonenzymatic glycosylation of hemo-globin is a result of increased blood glucose concentrations. In analogy glycosylated hemo-globin fractions were determined in 23 patients with hereditary fructose intolerance (HFI) and 8 patients with galactosemia (G) by means of hemoglobin chromatography on a column packed with Bio-Rex 70 resin. The concentrations were compared to those of 14 control patients and 43 patients with type 1 diabetes mellitus. Compared to controls, in HFI- and G-patients HbAlab was significantly increased. In contrast diabetic patients presented with a marked and significant increase of the HbAlc fraction. When purified hemoglobin was incubated with different monosaccharides respectively monosaccharide phosphates, an increase of HbAlab resulted mainly after galactose and fructose-1-phosphate. The determination of HbAlab in patients with HFI and G is considered a possible means of metabolic control.     

Verbal dyspraxia and galactosemia

Classical galactosemia is an autosomal recessive disorder resulting from deficient galactose-1-phosphateuridyl transferase (GALT) activity. Verbal dyspraxia is an unusual outcome in galactosemia. Here we validated a simplified breath test of total body galactose oxidation against genotype and evaluated five potential biochemical risk indicators for verbal dyspraxia in galactosemia: cumulative percentage dose (CUMPCD) of (13)CO(2) in breath, mean erythrocyte galactose-1-phosphate, highest erythrocyte galactose-1-phosphate, mean urinary galactitol, and erythrocyte GALT activity. Thirteen controls and 42 patients with galactosemia took a (13)C-galactose bolus, and the (CUMPCD) of (13)CO(2) in expired air was determined. Patients with <5% CUMPCD had mutant alleles that severely impaired human GALT enzyme catalysis. Patients with > or =5% CUMPCD had milder mutant human GALT alleles. Twenty-four patients consented to formal speech evaluation; 15 (63%) had verbal dyspraxia. Dyspraxic patients had significantly lower CUMPCD values (2.84 +/- 5.76% versus 11.51 +/- 7.67%; p < 0.008) and significantly higher mean erythrocyte galactose-1-phosphate (3.38 +/- 0.922 mg/dL versus 1.92 +/- 1.28 mg/dL; p = 0.019) and mean urinary galactitol concentrations (192.4 +/- 75.8 mmol/mol creatinine versus 122.0 +/- 56.4; p = 0.048) than patients with normal speech. CUMPCD values <5%, mean erythrocyte galactose-1-phosphate levels >2.7 mg/dL, and mean urinary galactitol levels >135 mmol/mol creatinine were associated with dyspraxic outcome with odds ratios of 21, 13, and 5, respectively. We conclude that total body oxidation of galactose to CO(2) in expired air reflects genotype and that this breath test is a sensitive predictor of verbal dyspraxia in patients with galactosemia.     

The diagnosis of hereditary fructose intolerance

Hereditary fructose intolerance (HFI) is a potentially life-threatening disorder and can be suspected from a detailed nutritional history. The usefulness of 2 diagnostic procedures, fructose tolerance test (FTT) and aldolase assay on biopsied liver, was studied. A standardized intravenous FTT with 200 mg/kg b.w. was done on 11 children with HFI, 17 age-matched contrast children, 6 adults with HFI and 6 adult controls. Blood glucose, phosphorus, urate, magnesium and fructose were followed for 2 hours. By the FTT, each HFI individual was reliably distinguished from controls and contrasts and even from those with acute liver disease other than HFI. Both children with non-HFI hepatopathy examined by both procedures had a normal FTT in spite of reduced liver fructaldolase activity. HFI children responded to the FTT by earlier and more pronounced hypoglycemia than adults, and one girl converted to an adult type response between the ages 12 and 181/2 years. Responses of two HFI sibling pairs and of one set of monozygotic twins were typical for age, but resemblance was no greater than within the unrelated HFI probands. The intravenous FTT is judged a reliable diagnostic tool, simple and harmless if done in hospital. Essential fructosuria is readily diagnosed by the FTT, but fructose-1,6-diphosphatase deficiency and HFI are not differentiated with certainty. Liver biopsies were obtained from 35 children with HFI, 14 contrast persons and 10 controls (of which 9 organ donors) and examined enzymatically. Deficiency of fructaldolase was observed in all HFI children but also in some contrast children suffering from acute liver disease other than HFI. In these, HFI could only be excluded when the reduced activity of reference enzymes such as fructose-1,6-diphosphatase and glucose-6-phosphatase and liver histology were included in the evaluation. In one deceased HFI infant, fructaldolase was deficient in both, liver and kidney cortex. Extent of antibody activation and of heat inactivation of residual fructaldolase varied between unrelated HFI patients but not within families. These results did not contribute to diagnosis but further documented genetic heterogeneity of HFI. For diagnosis of HFI we recommend 1. immediate elimination of fructose from the diet, 2. the intravenous FTT after several weeks of fructose withdrawal, and 3., should diagnosis still be uncertain, laparoscopic liver biopsy for assay of fructaldose and of reference enzymes and for histology.     

Supplemental calories improve essential fatty acid deficiency in cystic fibrosis patients

Fatty acid composition of plasma lipids was analyzed in malnourished cystic fibrosis patients undergoing 6 months of nutritional rehabilitation. There were three males and five females (mean age 15.1 yr); five patients had pancreatic insufficiency. Nutritional rehabilitation in seven of eight patients was accomplished by nocturnal nasogastric infusion of a high-carbohydrate semisynthetic diet, in addition to daily meals. One patient received high-energy food supplements as snacks in addition to regular meals. All patients were moderately to severely malnourished on entry to the study and showed significant improvement over the 6 months in (means +/- SE) energy intake (96 +/- 8.0 to 126 +/- 11% recommended daily allowance) and body composition (80 +/- 4 to 90 +/- 4% ideal body weight). Daily intakes of linoleic acid were not significantly different before or during nutritional rehabilitation either as an absolute amount (383 +/- 45 to 557 +/- 124 mg/kg/day) or as a percentage of total calories (4.50 +/- 0.40 to 4.73 +/- 0.14%). In comparison to the controls, the relative percentage of plasma cholesterol ester fatty acids of the CF patients on entry into the study showed a marked decrease of linoleic acid (52.7 +/- 1.0 versus 42.3 +/- 2.7%) with elevated palmitoleic (2.34 +/- 0.2 versus 5.64 +/- 0.7%) and oleic (18.7 +/- 1.0 versus 25.2 +/- 1.4%) acids; a pattern consistent with essential fatty acid deficiency. However, this pattern is not truly characteristic of a pure linoleic acid deficiency as the metabolites of linoleic acid were not decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hereditary fructose intolerance: A comprehensive review

Hereditary fructose intolerance (HFI) is a rare autosomal recessive inherited disorder that occurs due to the mutation of enzyme aldolase B located on chromosome 9q22.3. A fructose load leads to the rapid accumulation of fructose 1-phosphate and manifests with its downstream effects. Most commonly children are affected with gastrointestinal symptoms, feeding issues, aversion to sweets and hypoglycemia. Liver manifestations include an asymptomatic increase of transaminases, steatohepatitis and rarely liver failure. Renal involvement usually occurs in the form of proximal renal tubular acidosis and may lead to chronic renal insufficiency. For confirmation, a genetic test is favored over the measurement of aldolase B activity in the liver biopsy specimen. The crux of HFI management lies in the absolute avoidance of foods containing fructose, sucrose, and sorbitol (FSS). There are many dilemmas regarding tolerance, dietary restriction and occurrence of steatohepatitis. Patients with HFI who adhere strictly to FSS free diet have an excellent prognosis with a normal lifespan. This review attempts to increase awareness and provide a comprehensive review of this rare but treatable disorder.     

Glucose disturbances and regulation with glibenclamide in thalassemia

Specific laboratory and clinical characteristics indicate that the pathogenesis of diabetes in patients with thalassemia resembles the pathogenesis of maturity-onset diabetes (type II). Thus oral hypoglycemic agents may be used to regulate blood glucose levels by induction of insulin secretion and reduction of insulin resistance. The efficacy of glibenclamide administration in the management of glucose disturbances was evaluated in 33 patients with thalassemia, aged 12-30 years (mean 17.4 +/- 3.7), in whom diet and exercise failed to regulate hyperglycemia. The results were compared to 30 thalassemic patients (mean age 18.4 +/- 4.8 yr), who followed only diet and exercise. Improvement of OGTT was observed in 73% of the treated patients versus 43% of the control group for a mean period of 59 months. Deterioration of OGTT occurred more rapidly (33.7 +/- 26.1 vs 40.7 +/- 34.5 mos), and in more patients of the untreated group (57%) than in treated patients (27%). Among treated patients, effectiveness of oral hypoglycemic agents lasted longer in patients with diabetic (64.1 +/- 40.3 mos) than in patients with impaired curves (54.2 +/- 31 mos).     

Behavioral and neurotransmitter changes in the urease-infused rat: a model of congenital hyperammonemia

Rats implanted with subcutaneous or intraperitoneal osmotic minipumps infusing 0.8-1.25 IU urease/kg/h develop sustained hyperammonemia (range 137-497 microM, controls 88 +/- 51 microM +/- SD) for 5-7 days. Glutamine levels are also significantly elevated in plasma (677 +/- 166 versus 428 +/- 122 microM) and cerebral cortex (13.2 +/- 9.8 versus 4.7 +/- 2.8 nmol/mg tissue). Neurobehavioral abnormalities include decreased food intake and increased stereotypic activity. Increased serotonin turnover was suggested by elevated levels of tryptophan and 5-hydroxyindoleacetic acid in cerebral cortex, brain stem, and cerebellum of urease-infused compared to sham-operated animals. There were no changes in norepinephrine or gamma aminobutyric acid, and there was no correlation between the degree of hyperammonemia or glutaminemia and brain levels of tryptophan or biogenic amines. Animals receiving a tryptophan-deficient diet had significantly lower levels of tryptophan and 5-hydroxyindoleacetic acid in brain regions compared to animals receiving a normal tryptophan intake, under both control and hyperammonemic conditions. Despite the prevention of increased serotonin flux in hyperammonemic animals receiving a tryptophan-deficient diet, food intake and weight declined and there was increased stereotypic behavior.     

Stable isotope dilution analysis of galactitol in amniotic fluid: an accurate approach to the prenatal diagnosis of galactosemia

A stable isotope dilution assay for galactitol in amniotic fluid has been developed using selected ion monitoring chemical ionization gas chromatography-mass spectrometry of the hexaacetate derivative. [1,1-2H2]Galactitol was synthesized for use as the internal standard. Galactitol is a component of normal amniotic fluid with a mean concentration of 0.70 +/- 0.18 mumol/liter (n = 5). The amniotic fluid of a fetus with galactosemia had a concentration of 7.96 mumol/liter. Mannitol, sorbitol, and inositol were also found to be normal constituents of amniotic fluid. This stable isotope dilution assay is a rapid accurate method for measurement of galactitol in amniotic fluid for prenatal diagnosis of galactosemia.     

Evaluation of catecholamine metabolites, mIBG scan, and bone marrow cytology as response markers in stage 4 neuroblastoma

BACKGROUND: The early biological response has been proved an excellent predictor in acute lymphoblastic leukemia and nephroblastoma. We asked whether catecholamine metabolites, mIBG scan, and bone marrow evaluation might be relevant response markers in disseminated neuroblastoma. PROCEDURE: Three hundred sixty-seven unselected stage 4 neuroblastoma patients treated according the German cooperative trial NB90 were entered into the study. Catecholamine plasma and urine levels were centrally determined by gas chromatography/ mass spectrometry. Bone marrow cytology and mIBG scans were evaluated by local investigators. RESULTS: At diagnosis, mIBG scan was positive in 306 patients (92%), borderline in seven patients (2%), and negative in 19 patients (6%). Bone marrow aspirates were cytologically positive in 292 patients (84%) and negative in 57 patients (16%). Plasma catecholamine levels were elevated in 79% (206 of 260 patients.), urinary levels in 91% (307 of 338 patients). The outcome of patients with normalized mIBG scan after four courses of chemotherapy [5 year EFS (event free survival) 0.22 +/- 0.07] was not superior to the outcome of patients with still abnormal uptake (5 year EFS 0.30 +/- 0.05). The event free survival of patients with still positive bone marrow aspirates after four courses (0.16 +/- 0.06) was inferior to the EFS of patients with negative bone marrow aspirates (0.26 +/- 0.04, P = 0.0054). Urinary catecholamine normalization after four cycles of chemotherapy (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10) had no influence on outcome, whereas plasma catecholamine normalization after the first (5 year EFS 0.40 +/- 0.09 versus 0.14 +/- 0.07, P= 0.0364) or the fourth cycle (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10, P = 0.0242) indicated a better outcome. CONCLUSIONS: These data show that serial plasma catecholamine levels and bone marrow aspirates in the course of the disease are useful tools in predicting outcome.     

Effects of an early weaning on phosphate transport maturation in the rat kidney: influence of the phosphate content of the diet.

The renal phosphate (Pi) transport system matures during the 3rd postnatal wk in the rat by an increase in the carrier affinity for sodium-cotransported phosphate. This study examines the ability of pups to adapt their renal Pi transport to the dietary phosphorus content during this period of carrier affinity maturation, corresponding to the weaning period in the rat. Clearance experiments and brush border membrane studies were performed on 21-d-old rats weaned early on d 16 onto a low phosphate diet (LPD, 0.19 g/100 g), a normal phosphate diet (control, 0.78 g/100 g), or a high phosphate diet (HPD, 1.5 g/100 g). In LPD rats, the Pi fractional excretion (0.3 +/- 0.1%) was lower than in controls (18 +/- 3%, p < 0.001). It remained very low (0.21 +/- 0.05% in LPD rats versus 40.5 +/- 6.3% in controls, p < 0.001) after Pi perfusion (1.5 mumol.min-1.100 g-1) and the reabsorbed Pi per min, corrected for the glomerular filtration rate, was higher than in the two other groups. The calcium fractional excretion (12.6 +/- 1.02%) in the LPD rats was much higher than in the controls (0.42 +/- 0.2%, p < 0.001). In contrast, HPD rats had an elevated Pi fractional excretion (41 +/- 4%, p < 0.001), whereas reabsorbed phosphate per min corrected for the glomerular filtration rate was not increased by a Pi load.(ABSTRACT TRUNCATED AT 250 WORDS)     

ABNORMAL TYROSINE METABOLISM IN HEREDITARY FRUCTOSE INTOLERANCE

Elevated plasma tyrosine and methionine levels, together with excessive urinary excretion of p-hydroxypheny-acetic and -lactic acids were found in an infant with hereditary fructose intolerance (HFI). Such findings may be common in HFI and this diagnosis must be considered in any infant with biochemical abnormalities of tyrosine metabolism.     

Ophthalmic findings in classical galactosemia--a screened population

Classical galactosemia due to a deficiency of galactose-1-phosphate-uridyl transferase, is an autosomal recessive disorder of galactose metabolism with an incidence in Ireland of one in 30,000 births. It can result in cataract formation through the accumulation of galactitol within the lens. Seventeen children with transferase deficient galactosemia were studied. Early diagnosis followed by a galactose-free diet and tight biochemical control prevented cataract formation in 13 cases after a mean follow-up of 6.3 years. Cataracts did not regress in all patients commenced on diet by 6 weeks but early treatment prevented progression. The ophthalmologist may play an important role in the monitoring of patients with this disease as the recognition of new lens opacities by slit-lamp biomicroscopy may be the most sensitive initial index of inadequate biochemical control.     

Hereditary fructose intolerance and alpha(1) antitrypsin deficiency.

A patient with coexisting hereditary fructose intolerance (HFI) and alpha(1) antitrypsin deficiency (alpha(1)ATD) is described. Protease inhibitor typing was not conclusive, presumably because of impaired N-glycosylation secondary to HFI. The case underlines the diagnostic role of molecular genetic techniques in inborn errors of metabolism.     

Hereditary fructose intolerance and alpha(1) antitrypsin deficiency

A patient with coexisting hereditary fructose intolerance (HFI) and alpha(1) antitrypsin deficiency (alpha(1)ATD) is described. Protease inhibitor typing was not conclusive, presumably because of impaired N-glycosylation secondary to HFI. The case underlines the diagnostic role of molecular genetic techniques in inborn errors of metabolism.     

Beta 2-microglobulin levels in celiac disease

The serum levels of beta 2-microglobulins (beta 2-m) were studied in 65 celiac children. Significant statistical differences (p less than 0.05) were found between the values of patients on a gluten-containing diet (mean +/- SD, 1.92 +/- 0.64 mg/L) and those on a gluten-free diet for less than (mean +/- SD, 2.38 +/- 0.76 mg/L) or greater than (mean +/- SD, 1.46 +/- 0.77 mg/L) 8 months. A significant difference was also found between the first group and the 15-subject control group, who underwent intestinal biopsy for low stature or chronic diarrhea but had normal intestinal mucosa (mean +/- SD, 1.56 +/- 0.42 mg/L). Serum beta 2-m levels were above normal values (less than 2 mg/L) in 10 of 26 (38.5%) celiac patients on a gluten-containing diet and in two of 15 (13.3%) subjects of the control group. The beta 2-m values of patients on a gluten-free diet for less than or equal to 8 months were significantly different (p less than 0.001) from those of patients on a gluten-free diet for greater than 8 months, as well from those of the control group. No significant differences were found between patients on a gluten-free diet for greater than 8 months and the control group. A significant correlation between the antigliadin antibody (AGA) IgA and beta 2-m in the patients on a gluten-free diet for greater than 8 months and control-group patients was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical study of lymphoplasmacytic infiltrate and epithelial HLA-DR expression in the rectal and colonic mucosae of children with ulcerative colitis

Lymphocyte subpopulations, plasma cells in the lamina propria, and the expression of HLA-DR antigens on the epithelium of the rectal and colonic mucosae were studied in eight children with ulcerative colitis and 12 control subjects using a panel of monoclonal antisera and the peroxidase technique before any treatment and 3 months later (four patients). The numbers of intraepithelial lymphocytes were similar in specimens from patients and controls. The majority of these cells (on average, 73% in the patients and 84% in the controls) were mature CD3+ T cells; among them, CD8+ suppressor-cytotoxic cells were preponderant. In both untreated and treated patients, the numbers of mature T cells in the rectal mucosae were supranormal (1,870 +/- 205 cells/mm2, p less than 0.01 and 1,537 +/- 214 cells/mm2, p less than 0.05, respectively; controls, 1,105 +/- 214 cells/mm2). In rectal specimens from untreated patients, the number of helper T (CD4+) cells was increased (1,094 +/- 74 versus 801 +/- 74 cells/mm2, p less than 0.05); the same specimens had more B-1-positive (CD20+) B cells and pre-B cells (122 +/- 21 versus 71 +/- 17 cells/mm2, p less than 0.05). The number of IgG-containing cells was significantly greater than in the controls (1,058 +/- 263 versus 359 +/- 64 cells/mm2, p less than 0.01), and the commonest isotype in the plasma cells of patients was IgG. The number of IgE-containing cells was also significantly elevated (230 +/- 40 versus 95 +/- 16 cells/mm2, p less than 0.01). The numbers of IgA- and IgM-containing cells were similar in patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth in treated classical galactosemia patients

Decreased height and weight in treated children with classical galactosemia have been reported. However, growth has not been extensively studied. Patients might be at risk for an abnormal growth because of either disease-related intrinsic factors or diet-related factors. The objective was to gain insight in growth in treated children and adolescents with classical galactosemia. The studied population was a previously reported group of 40 classical galactosemia children. Prenatal growth was evaluated using length, weight and head circumference (HC) data from welfare centers or parents. Postnatal growth was evaluated using three height and weight measurements at baseline, 1 and 2 years to calculate growth velocities. Height Z-score was also corrected for target height Z-score (height Z-score divided by target height Z-score). Linear regression analysis was performed between growth velocities, IGF-I, IGFBP-3, dietary intake and galactose-1-phosphate-uridyltransferase activity. We found normal length (median 50.5 cm), weight (median 3,255 grams) and HC (median 33.9 cm) at birth. Mean height growth velocity was 0.87+/-1.2 for boys and -0.89+/-2.1 for girls, and mean weight growth velocity was 0.91+/-1.6 for boys and -0.74+/-1.3 for girls. Mean height corrected for target height was -1.5+/-0.9 in girls and -0.6+/-0.7 in boys. Height growth velocity was correlated with IGF-I (Pearson correlation= 0.499), IGFBP-3 (Pearson correlation 0.4) and height Z-scores corrected for target height Z-scores (Pearson correlation=0.550). Five children grew beyond the age of 18 years. In conclusion, prenatal growth was normal but postnatal growth was affected. Predicted final height is less than target height in most patients; however, target height might be reached for the children who grow beyond the age of 18. Decreased IGF-I and IGFBP-3 and or suboptimal hormonal replacement in girls might play a role.     

Anomalies héréditaires du métabolisme du galactose et du fructose

Galactose is present in the disaccharide lactose, main carbohydrate in milk. Three inborn errors of galactose metabolism are known. Galactokinase deficiency results in isolated nuclear cataract. Galactosemia is usaually due to galactose-1-phosphate uridyl transferase deficiency. This disease provokes hepatic, renal or ocular symptoms that improve with galactose free diet. Long-term prognosis is linked to its neurological consequences. UDP-galactose 4ʼ-epimerase deficiency is very rare and provokes either benign partial forms, or very rare profound deficiency giving severe forms of galactosemia. Fructose is a widely found hexose in human diet. Three inborn errors of metabolism may affect fructose metabolism. Fructokinase deficiency is an asymptomatic abnormality. Hereditary fructose intolerance, due to fructose aldolase deficiency provokes either acute gastrointestinal symptoms, with or without hypoglycemia, or hepatic or renal expressions that may be life threatening if a fructose free diet is not begun early. Fructose-1,6-diphosphatase deficiency is an inborn error affecting neoglucogenesis resulting in hypoglycemias with hyperlactacidemia.     

Treatment of hypercholesterolemia in children and adolescents

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)