Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively.

BACKGROUND: GLUT1 deficiency syndrome is caused by impaired glucose transport into the brain resulting in an epileptic encephalopathy, developmental delay, and a complex motor disorder. A ketogenic diet provides an alternative fuel to the brain and effectively restores brain energy metabolism. METHODS: Fifteen children with GLUT1 deficiency syndrome were enrolled prospectively for a 2.0 - 5.5-year follow-up of the effectiveness of a 3 : 1 LCT ketogenic diet. Eight patients enrolled were described previously, seven patients were novel. RESULTS: Four novel heterozygous GLUT1 mutations were identified. 10/15 patients remained seizure-free on the ketogenic diet in monotherapy. In 2/15 patients seizures recurred after 2(1/2) years despite adequate ketosis, but were controlled by add-on ethosuximide. In one patient seizures were reduced without complete seizure control. No serious adverse effects occurred and parental satisfaction with the diet was good. 2/15 patients discontinued the diet. CONCLUSION: GLUT1 deficiency syndrome represents a complex childhood encephalopathy that can be treated effectively by means of a ketogenic diet. The response to the diet did not correlate to clinical, biochemical, or genetic features of the disease. In contrast to previous reports, our results indicate that epilepsy is not always completely controlled by a ketogenic diet and can recur in a subset of patients.

[The ketogenic diet in German-speaking countries: update 2003]. / Die ketogene Diät in den deutschsprachigen Ländern im Jahr 2003: eine Standortbestimmung.

BACKGROUND: The ketogenic diet has been used for decades to treat intractable childhood epilepsies. It is also the treatment of choice for GLUT1 deficiency syndrome and pyruvate-dehydrogenase-complex-deficiency. Recent studies have once again confirmed the efficiacy of the diet, but the diet is hardly known in Europe and has never been quite accepted as an effective treatment of childhood epilepsy. PATIENTS: We report retrospective data on 146 children treated with the ketogenic diet in Austria, Switzerland, and Germany. METHOD: In 2000 and 2002, standardized questionaires were sent to 13 neuropediatric departments to evaluate indications, effects and side effects. RESULTS: In children with refractory epilepsy (n = 111), 8 % became seizure-free on the diet. Seizure reduction of > 90 % was achieved in additional 9 % of patients, a seizure reduction of 50-90 % in additional 14 % of patients. There was a great variability between epilepsy departments. All patients with GLUT1 deficiency syndrome (n = 18) and pyruvate-dehydrogenase-complex-deficiency (n = 15) showed clinical improvement. In GLUT1 deficiency syndrome, complete seizure control was achieved in 94 % of patients. Compliance was good in 82 % of all patients regardless of the indication for the diet. CONCLUSION: In contrast to the general restraint towards the ketogenic diet in Europe, our data supports its effectiveness as the treatment of choice for GLUT1-deficiency syndrome und pyruvate-dehydrogenase-complex-deficiency. In children with refractory epilepsy, the ketogenic diet matched the effect of most anticonvulsants and was well tolerated. These data and two workshops resulted in recommendations for the use of the ketogenic diet in children as a basis for a general diagnostic and therapeutic standards to compare and improve the use of the ketogenic diet in Europe.

Introduction of a ketogenic diet in young infants.

The ketogenic diet is a rational treatment for pyruvate dehydrogenase complex deficiency (McKusick 312170) and GLUT1 deficiency syndrome (McKusick 138140). An increasing number of patients are diagnosed in early infancy, but few data are available on the introduction of a ketogenic diet in this age group. GLUT1 deficiency syndrome was suspected in four infants presenting with seizures and unexplained hypoglycorrhachia. A ketogenic diet was introduced at 6-28 weeks of age. Ketosis was initiated by fasting, monitored by bedside blood glucose and 3-hydroxybutyrate determinations, and was maintained successfully using supplemented carbohydrate-free infant formula and emulgated triglycerides. All patients developed ketosis within 24 h. 3-Hydroxybutyrate concentrations available at the bedside correlated inversely with the base excess. At glucose levels < or = 40 mg/dl patients remained asymptomatic in the presence of ketones. The ketogenic formula was tolerated well, parental compliance was good, and all patients remained seizure-free on the diet. GLUT1 deficiency was confirmed in two patients; the diet was discontinued in the other two patients. In one infant, failure to thrive on medium-chain triglycerides was effectively reversed using long-chain triglycerides. Urine dipstick analyses failed to detect ketosis in another infant. Adverse effects of the diet were limited to renal stones in one patient. The ketogenic diet can be introduced and maintained successfully in young infants using long-chain fat emulsion. Monitoring 3-hydroxybutyrate at the bedside was useful for metabolic control and superior to urine dipstick analysis. Seizure control was effective and adverse effects were limited, but evaluation of the long-term effects of the ketogenic diet in this age group must await ongoing studies.

Colorectal adenomas and diet: a case-control study. Colorectal Adenoma Study Group.

It has been postulated that high intakes of animal fat and protein and low intakes of fiber, calcium, and antioxidants increase the risk of colorectal cancer. Whether specific types of protein such as that from red meat are important, and whether vegetables might be key protective factors will also be considered in this study. Dietary intake over the past year was studied according to the diet history method by means of a case-control study in 184 cases and matched controls. After adjustment for energy, relative weight, and social class, no associations were found for fat or protein in comparison with either control group. Unexpectedly, carbohydrate intake was inversely related with adenoma risk, the RR being 0.29 (0.10-0.81) for quintile 5 versus 1 in comparison with hospital controls. None of the antioxidants showed a significant protective effect except beta-carotene intake in comparison with hospital controls, the RR being 0.24 (0.11-0.50) for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile of intake being 3.6 (1.7-7.5) in comparison with hospital controls and 4.4 (1.6-12.1) in comparison with population controls. Our data support the protective role for carbohydrate intake and of beta-carotene intake in the etiology of colorectal adenomas and show a strong increased risk for developing adenomas in those with high meat intake.

Relation of serum antioxidant vitamins to the risk of colorectal adenoma.

The relation between risk of colorectal adenoma and serum concentrations of vitamins A, C, E and carotene was examined in a population-based case-control study of 105 cases of colorectal adenoma and a similar number of hospital controls showing no polyps at colonoscopy and a second control group of population controls. There were no significant associations with serum concentrations of vitamins C and E and carotene. Serum concentrations of vitamin A were significantly inversely related to the risk of colorectal adenoma when cases were compared with both control groups. After adjustment for energy intake, smoking, alcohol, estrogen therapy, body-mass-index and social class the inverse association between vitamin A and colorectal adenoma was even more marked. For the highest versus the lowest quartile of serum levels the adjusted RR was 0.23 (0.07-0.73) in relation to hospital controls and 0.08 (0.02-0.25) in relation to population controls. These findings suggest that the risk of developing colorectal adenomas is reduced in those with high vitamin A levels.

Alcohol and cigarette smoking and the risk of colorectal adenomas.

Whether alcohol and tobacco can be considered as risk factors for the occurrence of adenomas remains inconclusive. A case-control study was carried out to examine these factors while taking into account possible confounding factors. One hundred eighty-two patients with colorectal adenomas and similar numbers of hospital and population controls were compared as to intake of alcohol and various nutrients including smoking and drug intake. There was a positive association between cigarette smoking and adenoma risk compared with hospital controls, the RR being 2.3 (1.1-4.6). Overall alcohol intake was no risk factor in hospital controls, but drinking liquor was associated with an increased risk, the RR being 4.1 (1.3-13.4) and was especially marked in males [RR 10.2 (2.3-46.2)]. Compared with population controls, there was no increased RR associated with smoking or alcohol intake. None of the risk factors was positively associated with disease risk in those with small or large adenomas. These findings suggest that alcohol and tobacco play no major role in the formation or growth of adenomas.

Long-term use of nonsteroidal antiinflammatory drugs and the risk of colorectal adenomas. The Colorectal Adenoma Study Group.

AIMS: Previous studies have suggested that the regular use of NSAIDs reduces the risk of colorectal adenomas. The aim of this study was to examine this association while taking possible confounding factors into account. METHODS: The intake of drugs including NSAID intake during the last 20 years was assessed by means of a case-control study in 184 cases and matched hospital and community controls. RESULTS: Overall, there were few individuals with a relevant drug intake for more than 5 years. NSAID intake for more than five years was associated with decreased risk in comparison with both control groups. The RR was 0.20 (0.04-1.04) compared with hospital and 0.21 (0.04-0.99) compared with population controls, the latter association being statistically significant. Subgroup analysis by type of drug revealed a significant protective effect only for long-term aspirin intake in relation to hospital controls, the RR being 0.09 (0.01-0.82). CONCLUSION: Our data support the hypothesis that there is a protective effect of NSAID intake of more than 5 years against the development of colorectal polyps.

Helicobacter pylori and the risk of colonic adenomas. Colorectal Adenoma Study Group.

AIMS: Previous studies have found a positive association between Helicobacter pylori infection and colorectal adenomas. The aim of the present study was to examine this association while taking possible confounding factors into account. METHODS: 98 serum samples were available from 182 patients with colorectal adenomas who entered a case-control study of colorectal adenomas and diet. The H. pylori status in patients was compared with a hospital control group and a population control group. RESULTS: H. pylori IgG antibodies were more common in colorectal polyp patients compared with either control group, the prevalence being 79% in cases compared with 62% in both control groups. The corresponding RR was 1.4 (0.76-2.6) compared with hospital controls and 2.1 (1.1-3.9) compared with population controls. After adjusting for possible confounding variables the association between H. pylori status and adenoma risk was even more marked. There was an RR of 1.6 (0.80-3.4) compared with hospital controls and an RR of 2.6 (1.3-5.4) compared with population controls, the latter association being statistically significant. CONCLUSION: These findings suggest a statistically significant association between H. pylori infection and colorectal polyps. A possible mechanism might be increased gastrin levels in H. pylori-infected subjects which exhibit a trophic effect on colonic mucosa.