Background: The ketogenic diet (KD) is an effective treatment against drug-resistant epilepsy in children. The KD is a diet rich in fats that produces anticonvulsant and neuroprotective effects that reduces seizures and improves the cognitive state. Nevertheless, it can produce side effects that sometimes can be serious. Further, the effect on growth is quite controversial when used for an extended period of time. The aim of this paper was to assess the effectiveness, side effects, and repercussions in the development of children who have been treated with a KD for more than 2 years. Methods: Observational descriptive study of 26 pediatric patients on a KD, with data collection at baseline, at 3, 6, and 12 months, and then once a year. Number of seizures, type of seizures, anti-seizure drugs, anthropometry, side effects, and alterations in laboratory assessment were monitored. Results: In every assessment, about 60%–75% of the patients experienced a reduction in number of seizures of over 90%, and at least 50% experienced side effects, of which digestive issues, alteration in the lipid metabolism, and hypercalciuria were the most common. The KD significantly affected height after 2 years of treatment. Conclusions: The KD is an effective treatment for drug-resistant epilepsy. Its side effects, although common, are very mild; therefore, this constitutes a very safe treatment for children of all ages. More studies are needed to identify and prevent potential causes of growth retardation in children on the KD.

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. Methods: An observational descriptive study was conducted to describe 18 children (January 2009–August 2020). SLC2A1 analysis, seizures, movement disorder, anti-epileptic drugs (AEDS), anthropometry, SE, and laboratory assessment were monitored baseline and at 3, 6, 12, and 24 months after the onset of KDT. Results: 6/18 were SLC2A1(+) and 13/18 had seizures. In these groups, the age for debut of symptoms was higher. The mean time from debut to KDT onset was higher in SLC2A1(+). The modified Atkins diet (MAD) was used in 12 (5 SLC2A1(+)). Movement disorder improved (4/5), and a reduction in seizures >50% compared to baseline was achieved in more than half of the epileptic children throughout the follow-up. No differences in effectiveness were found according to the type of KDT. Early SE occurred in 33%. Long-term SE occurred in 10, 5, 7, and 5 children throughout the follow-up. The most frequent SE were constipation, hypercalciuria, and hyperlipidaemia. No differences in growth were found according to the SLC2A1 mutation or type of KDT. Conclusions: CKD and MAD were effective for SLC2A1 positive and negative patients in our cohort. SE were frequent, but mild. Permanent monitoring should be made to identify SE and nutritional deficits.

Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 ± 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 ± 102.1 mg/kg/day dose, compared to 262.6 ± 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 ± 59 days), a statistically significant reduction in ammonia (from 40.2 ± 17.3 to 32.6 ± 13.9 μmol/L, p < 0.001) and glutamine levels (from 791.4 ± 289.8 to 648.6 ± 247.41 μmol/L, p < 0.001) was observed. After one year of GPB treatment (411 ± 92 days), we observed an improved metabolic control (maintenance of ammonia and glutamine reduction, with improved branched chain amino acids profile), and a reduction in hyperammonemic crisis rate (from 0.3 ± 0.7 to less than 0.1 ± 0.3 crisis/patients/year, p = 0.02) and related adverse effects (RAE, from 0.5 to less than 0.1 RAEs/patients/year p < 0.001). Conclusions: This study demonstrates the safety of direct switching from other nitrogen scavengers to GPB in clinical practice, which improves efficacy, metabolic control, and RAE compared to previous treatments.

Hereditary Fructose Intolerance (HFI) is an autosomal recessive inborn error of metabolism characterised by the deficiency of the hepatic enzyme aldolase B. Its treatment consists in adopting a fructose-, sucrose-, and sorbitol (FSS)-restrictive diet for life. Untreated HFI patients present an abnormal transferrin (Tf) glycosylation pattern due to the inhibition of mannose-6-phosphate isomerase by fructose-1-phosphate. Hence, elevated serum carbohydrate-deficient Tf (CDT) may allow the prompt detection of HFI. The CDT values improve when an FSS-restrictive diet is followed; however, previous data on CDT and fructose intake correlation are inconsistent. Therefore, we examined the complete serum sialoTf profile and correlated it with FSS dietary intake and with hepatic parameters in a cohort of paediatric and adult fructosemic patients. To do so, the profiles of serum sialoTf from genetically diagnosed HFI patients on an FSS-restricted diet (n = 37) and their age-, sex- and body mass index-paired controls (n = 32) were analysed by capillary zone electrophoresis. We found that in HFI patients, asialoTf correlated with dietary intake of sucrose (R = 0.575, p < 0.001) and FSS (R = 0.475, p = 0.008), and that pentasialoTf+hexasialoTf negatively correlated with dietary intake of fructose (R = −0.386, p = 0.024) and FSS (R = −0.400, p = 0.019). In addition, the tetrasialoTf/disialoTf ratio truthfully differentiated treated HFI patients from healthy controls, with an area under the ROC curve (AUROC) of 0.97, 92% sensitivity, 94% specificity and 93% accuracy.

Ketogenic dietary therapies (KDT) produce anticonvulsant and neuroprotective effects, reduce seizures and improve the cognitive state in patients with epilepsy. Our purpose was to evaluate the effects of KDT in children with refractory epilepsy (effectiveness, side effects, impact on nutritional status and growth). A retrospective and prospective observational descriptive study was conducted in a Spanish tertiary hospital (January 2000 to December 2018). One hundred sixty pediatric patients with epilepsy were treated with KDT (82 males; mean age 5 years 9 months). Seizures, anti-epileptic drugs, anthropometric measures, side effects, and laboratory assessment were monitored baseline and at 3, 6, 12 and 24 months after the onset of KDT. In these time intervals, the seizure-free patients were: 13.7, 12.5, 14.4 and 10.6%, respectively, and a reduction of seizures≥50% was achieved in 41.9, 37.5, 28.7 and 16.2%. Side effects were frequent, especially digestive disorders, hypercalciuria, hypoglycemia, hepatic dysfunction and dyslipidemia. Prealbumin, retinol binding protein, vitamin A and magnesium decreased significantly. Height was affected, especially in children below 2 years. KDT are effective for refractory epilepsy in children. However, adverse effects are frequent, and it may affect nutritional status and growth.

Linked Content This article is linked to Philpott et al papers. To view these articles, visit https://doi.org/10.1111/apt.14573 and https://doi.org/10.1111/apt.15292.