Clinical Features and Genetic Sequencing of Children with Fanconi-Bickel Syndrome.

The present paper reports 10 patients (9 families) with Fanconi-Bickel syndrome managed during 2010-2021. Patients presented with polyuria, polydipsia, hepatomegaly, rickets, and stunting at a median of 5 (3, 7.3) mo; one had transient neonatal diabetes. Glucosuria, generalized aminoaciduria, ß2-microglobinuria, urinary phosphate wasting, and hypercalciuria were present in all patients; 3 patients had nephrocalcinosis. Other metabolic abnormalities included hypertriglyceridemia (n = 5/6), fasting hypoglycemia (n = 5/8), and postprandial hyperglycemia (n = 3/6). Genetic analysis showed 7 homozygous or compound heterozygous variants in SLC2A2. A pathogenic variant c.952G>A, common to 4 patients (3 families), might be a potential hotspot. At a median follow-up of 43 mo, 4 patients died at a median of 25 mo; short stature persisted in all except one patient who showed catch-up growth with uncooked corn-starch diet. The present findings suggest that the Fanconi-Bickel syndrome has a severe phenotype with an unsatisfactory outcome. A high index of suspicion for diagnosis and efforts for facilitation of dietary therapy are necessary.

A Pilot Randomised Controlled Trial Examining the Benefit of a Neutropenic Diet for Children Undergoing Cancer Treatment.

Neutropenic diet(ND) has been hypothesized to decrease the rate of febrile neutropenia(FN) occurring post-chemotherapy for pediatric cancers. Despite widespread use, it has not shown to be of benefit by randomized controlled trials(RCT) in western countries. No RCT has been conducted in India/LMIC to evaluate its efficacy against the standard Indian diet. Forty-two(42) children, aged 3-14 y, with cancer, scheduled to receive strongly myelosuppressive chemotherapy were randomized to receive either neutropenic diet(n = 21) or standard Indian diet(n = 21) for one chemotherapeutic cycle. FN rate was recorded as the primary outcome while the focus of infection, antibiotic length, the requirement for hospital admission, adherence to diet were the secondary outcomes. The groups were similar in baseline characteristics. Twelve patients (57%) in the neutropenic diet and nine patients(43%) in the standard diet arm developed FN. Patients in ND-arm had significantly higher chance of getting neutropenic enterocolitis(NEC) (33.33% vs 4.76% p = 0.044). Mortality (14.29%vs 0%, p = 0.23) and requirement for admission (47.6%vs 19.05%, p = 0.06), was more in the ND-arm but statistically non-significant. There was no significant difference in antibiotic length. Adherence was similar in both groups (95% vs 98%). Neutropenic diet was not effective in reducing FN rate and was associated with higher rate of NEC when compared to the standard diet.

Medical nutrition therapy of pediatric type 1 diabetes mellitus in India: Unique aspects and challenges.

Medical nutrition therapy (MNT) is a vital aspect of management of type 1 diabetes mellitus (T1DM) and should be tailored to ethnic and family traditions and the socioeconomic and educational status of the patient. In this article, we discuss the unique aspects of MNT in children and adolescents with T1DM in the Indian setting, with focus on the challenges faced by patients, dieticians and physicians and how these can be overcome. The authors reviewed the available literature on MNT in T1DM from India and prepared the document based on their vast collective clinical experience in treating patients with T1DM from different regions in India. Indian diets are predominantly carbohydrate-based with high glycemic index (GI) and low protein content. Various methods are available to increase the protein and fiber content and reduce the GI of food in order to limit glycemic excursions. Insulin regimens need to be tailored to the child's school timings, meal schedule, and the availability of a responsible adult to supervise/administer insulin. All patients, irrespective of economic and education background, should be taught the broad principles of healthy eating, balanced diet and carbohydrate counting. There are various barriers to dietary compliance, including joint family system, changing lifestyles, and other factors which need to be addressed. There is a need to customize dietary management according to patient characteristics and needs and develop standardized patient educational material on principles of healthy eating in various regional languages.

Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low Glycemic Index Therapy Diet Among Children With Drug-Resistant Epilepsy: A Randomized Clinical Trial.

Importance: The ketogenic diet (KD) has been used successfully to treat children with drug-resistant epilepsy. Data assessing the efficacy of the modified Atkins diet (MAD) and low glycemic index therapy (LGIT) diet compared with the KD are scarce. Objective: To determine whether the MAD and LGIT diet are noninferior to the KD among children with drug-resistant epilepsy. Design, Setting, and Participants: One hundred seventy children aged between 1 and 15 years who had 4 or more seizures per month, had not responded to 2 or more antiseizure drugs, and had not been treated previously with the KD, MAD, or LGIT diet were enrolled between April 1, 2016, and August 20, 2017, at a tertiary care referral center in India. Exposures: Children were randomly assigned to receive the KD, MAD, or LGIT diet as additions to ongoing therapy with antiseizure drugs. Main Outcomes and Measures: Primary outcome was percentage change in seizure frequency after 24 weeks of dietary therapy in the MAD cohort compared with the KD cohort and in the LGIT diet cohort compared with the KD cohort. The trial was powered to assess noninferiority of the MAD and LGIT diet compared with the KD with a predefined, noninferiority margin of -15 percentage points. Intention-to-treat analysis was used. Results: One hundred fifty-eight children completed the trial: KD (n = 52), MAD (n = 52), and LGIT diet (n = 54). Intention-to-treat analysis showed that, after 24 weeks of intervention, the median (interquartile range [IQR]) change in seizure frequency (KD: -66%; IQR, -85% to -38%; MAD: -45%; IQR, -91% to -7%; and LGIT diet: -54%; IQR, -92% to -19%) was similar among the 3 arms (P = .39). The median difference, per intention-to-treat analysis, in seizure reduction between the KD and MAD arms was -21 percentage points (95% CI, -29 to -3 percentage points) and between the KD and LGIT arms was -12 percentage points (95% CI, -21 to 7 percentage points), with both breaching the noninferiority margin of -15 percentage points. Treatment-related adverse events were similar between the KD (31 of 55 [56.4%]) and MAD (33 of 58 [56.9%]) arms but were significantly less in the LGIT diet arm (19 of 57 [33.3%]). Conclusions and Relevance: Neither the MAD nor the LGIT diet met the noninferiority criteria. However, the results of this study for the LGIT diet showed a balance between seizure reduction and relatively fewer adverse events compared with the KD and MAD. These potential benefits suggest that the risk-benefit decision with regard to the 3 diet interventions needs to be individualized. Trial Registration: ClinicalTrials.gov Identifier: NCT02708030.

EFFECT OF GLUTEN-FREE DIET ON METABOLIC CONTROL AND ANTHROPOMETRIC PARAMETERS IN TYPE 1 DIABETES WITH SUBCLINICAL CELIAC DISEASE: A RANDOMIZED CONTROLLED TRIAL.

Objective: It is unclear whether the institution of gluten-free diet (GFD) is beneficial in patients with type 1 diabetes (T1DM) and subclinical celiac disease (CD). Our primary objective was to evaluate the effect of GFD on the frequency of hypoglycemia, in patients with T1DM and subclinical CD. Our secondary objective was to investigate the effect of GFD on height, weight, glycosylated hemoglobin (HbA1c), insulin dose requirement, and bone mineral homeostasis. Methods: We carried out a prospective open label randomized controlled trial (RCT). Patients with T1DM and subclinical CD were randomized to receive GFD or a normal diet for 1 year. The primary outcome was the frequency of hypoglycemic episodes (blood glucose <70 mg/dL) measured by self-monitoring of blood glucose (SMBG) at the sixth month of the study in the 2 groups. Results: Screening for CD was carried out in 320 T1DM patients. Thirty eligible patients were randomized to receive GFD (n = 15) or a normal diet (n = 15). The mean number of hypoglycemic episodes/month recorded by SMBG and the mean time spent in hypoglycemia measured by CGM (minutes) in the GFD group versus the non-GFD group at six months was 2.3 minutes versus 3.4 minutes (P = .5) and 124.1 minutes versus 356.9 minutes (P = .1), respectively. The mean number of hypoglycemic episodes/month significantly declined in the GFD group (3.5 episodes at baseline versus 2.3 episodes at the sixth month; P = .03). The mean HbA1c declined by 0.73% in the GFD group and rose by 0.99% in non-GFD group at study completion. Conclusion: This is the first RCT to assess the effect of GFD in T1DM and subclinical CD. A trend towards a decrease in hypoglycemic episodes and better glycemic control was seen in patients receiving GFD. Abbreviations: BMC = bone mineral content; BMI = body mass index; CD = celiac disease; CGM = continuous glucose monitoring; GFD = gluten-free diet; Hb = hemoglobin; HbA1c = glycosylated hemoglobin; iPTH = intact parathyroid hormone; RCT = randomized controlled trial; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus; tTG-IgA = tissue transglutaminase immunoglobulin A.

Adiponectin, Interleukin-6 and High-sensitivity C-reactive Protein Levels in Overweight/Obese Indian children.

OBJECTIVE: The aim of our study was to assess serum Adiponectin, Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) levels and their correlation with conventional risk factors for cardiovascular disease and diabetes in overweight/obese Indian children. METHODS: Body mass index (BMI), waist circumference, blood pressure, fasting serum adiponectin, IL-6, hsCRP, blood glucose, triglycerides, and total and high density lipoprotein cholesterol were measured in children aged 7-15 years with BMI >85th centile. RESULTS: 84 overweight/obese children (48 boys) with mean (SD) age 10.2 (1.9) years were enrolled. Mean (SD) adiponectin, hsCRP and median (IQR) IL-6 levels were 6.0 (3.1) µg/mL, 3.4 (2.4) mg/L and 12.7 (5.0-90.0) pg/mL, respectively. Low adiponectin, high hsCRP and high IL-6 were noted in 16.5%, 49.4% and 54.4% participants, respectively. Adiponectin was inversely correlated with waist circumference, and IL-6 positively with BMI and blood glucose. CONCLUSION: Inflammatory mediators, hsCRP and IL-6 were elevated in half of the overweight children. Adiponectin and IL-6 correlated well with traditional risk markers.

Ambulatory Blood Pressure Monitoring in Frequently Relapsing Nephrotic Syndrome.

OBJECTIVES: To screen patients with frequently relapsing nephrotic syndrome (FRNS) for the presence of ambulatory hypertension and left ventricular hypertrophy. METHODS: Following ethical and parental approvals, consecutive patients with FRNS of ≥2 y duration were enrolled. Those with estimated glomerular filtration rate <60 ml/min/1.73 m2 and known familial hypercholesterolemia or diabetes mellitus were excluded. Clinic blood pressure was measured by oscillometry and 24-h ambulatory blood pressure was recorded by Spacelab 90207; echocardiography was done for left ventricular mass. Ambulatory hypertension was defined as the presence of clinic blood pressure >95th centile for age, sex and height, and systolic blood pressure load exceeding 25 %. RESULTS: Of 99 patients, 73 were boys; their median (IQR) age was 120 (84-156) mo. Clinic blood pressure was >95th percentile in 63 (63.6 %) patients. Ambulatory hypertension was present in 33 (33.3 %), including 14 patients with severe hypertension; 16 (16.1 %) had masked hypertension and 30 (30.3 %) had white coat hypertension. Non-dipping was seen in 72 and 55 patients had high nocturnal systolic blood pressure load. Of 21 patients with increased left ventricular mass index, 9 (42.9 %) had ambulatory hypertension, 3 (14.3 %) had masked hypertension and 6 (28.6 %) patients had white coat hypertension. Compared to those with normal blood pressure, patients with ambulatory hypertension were younger at onset of nephrotic syndrome (odds ratio, OR 0.94; 95 % CI 0.91-0.98; P = 0.002), longer duration of frequently relapsing disease (OR 1.05; 95 % CI 1.00-1.10; P = 0.034) and higher body mass index (BMI) (OR 1.61; 95 % CI 1.07-4.40; P = 0.020). BMI was positively correlated with 24-h systolic blood pressure load (r = 0.23; P = 0.002) and with the left ventricular mass index (r = 0. 57; P = 0.001). CONCLUSIONS: Many patients with FRNS showed high prevalence of clinic, ambulatory and white coat hypertension, emphasizing the need to carefully screen these patients in order to ensure their appropriate management. While clinic blood pressure monitoring detects most patients with hypertension, it misses a significant proportion with masked hypertension, underscoring the need for ambulatory blood pressure monitoring and screening for end organ damage. High BMI was the chief risk factor for hypertension, suggesting that control of overweight and hypertension might improve cardiovascular outcomes.

Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial.

PURPOSE: This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy. METHODS: This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2-14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989). RESULTS: Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with>50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, p<0.0001). The proportion of children with 90% seizure reduction was also higher in the diet group (19.5% vs 2%, p=0.09). Six children in the diet group were seizure free at 3 months compared with two in the control group (p=0.26). At 3 months, 6 children had constipation and 5 had weight loss. CONCLUSION: A simplified version of the modified Atkins diet was developed for use by parents with low levels literacy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy.

Glutaric Acidemia Type 1-Clinico-Molecular Profile and Novel Mutations in GCDH Gene in Indian Patients.

Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited metabolic disorders. Macrocephaly, acute encephalitis-like crises, dystonia and characteristic frontotemporal atrophy are the hallmarks of this disease. In this communication, we present the clinical, biochemical and molecular profile of seventeen GA I patients from 15 unrelated families from India and report seven novel mutations in GCDH gene (c.281G>A (p.Arg94Gln), c.401A>G (p.Asp134Gly), c.662T>C (p.Leu221Pro), c.881G>C (p.Arg294Pro), c.1173dupG (p.Asn392Glufs*5), c.1238A>G (p.Tyr413Cys) and c.1241A>C (p.Glu414Ala)). Out of these, c.662T>C (p.Leu221Pro) in exon 8 and c.281G>A (p.Arg94Gln) allele in exon 4 were low excretor alleles, whereas c.1241A>C (p.Glu414Ala), c.1173dupG and c.1207C>T (p.His403Tyr) in exon 11 were high excretor alleles. We conclude that c.1204C>T (p.Arg402Trp) is probably the most common mutant allele. Exons 11 and 8 are the hot spot regions of GCDH gene in Indian patients with GA I. An early diagnosis and timely intervention can improve the underlying prognosis. Molecular confirmation is helpful in providing genetic counselling and prenatal diagnosis in subsequent pregnancy.

Use of the modified Atkins diet in Lennox Gastaut syndrome.

There is scanty data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. This study was a retrospective review of children with Lennox-Gastaut syndrome treated with the modified Atkins diet from May 2009 and March 2011. The diet was initiated in those children who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Twenty-five children were started on a modified Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2 patients were seizure-free, and 10/25 children had >50% reduction in seizure frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50% reduction in seizure frequency. The side effects of the diet were mild. The modified Atkins diet was found to be effective and well tolerated in children with Lennox-Gastaut syndrome.

Use of the modified Atkins diet for treatment of refractory childhood epilepsy: a randomized controlled trial.

PURPOSE: The aim of this study was to evaluate the efficacy of the modified Atkins diet in a randomized controlled trial in children with refractory epilepsy. METHODS: Children aged 2-14 years who had daily seizures despite the appropriate use of at least three anticonvulsant drugs were enrolled. Children were randomized to receive either the modified Atkins diet or no dietary intervention for a period of 3 months. The ongoing anticonvulsant medications were continued unchanged in both the groups. Seizure control at 3 months was the primary end point. Analysis was intention to treat. Adverse effects of the diet were assessed by parental reports (ClinicalTrials.gov Identifier: NCT00836836). KEY FINDINGS: Among a total of 102 children, 50 were in the diet group and 52 in the control group. Four children discontinued the diet before the study end point, and three children in the control group were lost to follow-up. The mean seizure frequency at 3 months, expressed as a percentage of the baseline, was significantly less in the diet group: 59 ± 54 (95% confidence interval [CI] 44-74.5) versus 95.5 ± 48 (95% CI 82-109), p = 0.003. The proportion of children with >90% seizure reduction (30% vs. 7.7%, p = 0.005) and >50% seizure reduction was significantly higher in the diet group (52% vs. 11.5%, p < 0.001). Constipation was the most common adverse effect among children on the diet (23, 46%). SIGNIFICANCE: The modified Atkins diet was found to be effective and well tolerated in children with drug-refractory epilepsy.

Use of the modified Atkins diet in infantile spasms refractory to first-line treatment.

This prospective, open label, uncontrolled study was performed to evaluate the efficacy and tolerability of the modified Atkins diet in children with refractory infantile spasms. Fifteen consecutive children aged six months to three years having daily infantile spasms in clusters with electroencephalographic evidence of hypsarrhythmia despite treatment with hormonal treatment (oral corticosteroids/adrenocorticotrophic hormone) and/or vigabatrin, and at least one additional anti-epileptic drug were enrolled. Children with known or suspected inborn errors of metabolism or systemic illnesses were excluded. Carbohydrate intake was restricted to ten grams/day. Among these 12 boys and three girls (median age-24 months), 13 had symptomatic etiology. After three months of diet, six children were spasm free. The time to spasm freedom after diet initiation ranged from two days to two months. The most frequent adverse effect observed was constipation. The modified Atkins diet was found to be effective and well tolerated in children with refractory infantile spasms (ClinicalTrials.gov identifier: NCT01006811).

Serum magnesium in overweight children.

OBJECTIVE: To determine whether overweight children and adolescents have lower serum concentration and lower dietary intake of magnesium compared to those with normal weight; and to study the correlation of serum magnesium levels with components of metabolic syndrome in children and adolescents. DESIGN: Cross-sectional, comparative study. SETTING: General/Pediatric Endocrinolgy OPD tertiary care medical centre. Study done from July 2007 to March 2009 PARTICIPANTS: 55 overweight and 53 normal weight children and adolescents aged 4 years to 14 years. METHODS: We compared fasting levels of serum magnesium, insulin, glucose, total and HDL-cholesterol, triglycerides and dietary magnesium intake. RESULTS: The serum magnesium levels were significantly lower in overweight (2.12 ±; 0.33 mg/dL) compared to normal weight group (2.56 ± 0.24 mg/dL, P<0.001), while the dietary intake of magnesium (adjusted for calorie intake) was higher in overweight group (0.20 ± 0.06 mg/kcal) compared to normal weight (0.17 ± 0.05 mg/kcal; P= 0.005). Serum magnesium levels were inversely correlated with body mass index, systolic blood pressure, diastolic blood pressure, waist circumference and fasting insulin levels. CONCLUSIONS: Serum magnesium levels were significantly lower in overweight children compared to those with normal weight in spite of a higher dietary intake.

Efficacy of 4:1 (classic) versus 2.5:1 ketogenic ratio diets in refractory epilepsy in young children: a randomized open labeled study.

PURPOSE: The ketogenic (lipid to non-lipid) ratio may play an important role in the efficacy and tolerability of ketogenic diets (KD). This study was planned to compare the efficacy and tolerability of 2.5:1 versus 4:1 lipid:non-lipid ratio KD in young children with refractory epilepsy. METHODS: Children aged 6 months to 5 years with refractory epilepsy were enrolled. They were randomized to receive either a 4:1 or 2.5:1 ketogenic ratio diet, which was introduced using a non-fasting protocol. Seizure frequency, biochemical profile (liver and kidney function tests, fasting lipid profile, and spot urinary calcium-creatinine ratio), and adverse effects were recorded at three months in both groups. RESULTS: Thirty eight children were enrolled, 19 in each group. At three months, 11 children (58%) in the 4:1 group and 12 (63%) in the 2.5:1 group had more than 50% reduction in seizures (p=0.78). Five children (26%) in the 4:1 group and four (21%) in 2.5:1 group became seizure free. There was no significant difference in the biochemical parameters between the two groups. CONCLUSION: 2.5:1 ratio KD is possibly as effective as 4:1 KD in controlling seizures and has fewer adverse effects.

Seizure control and biochemical profile on the ketogenic diet in young children with refractory epilepsy--Indian experience.

AIM: This study evaluated the efficacy and tolerability of the ketogenic diet (KD) in young Indian children with refractory epilepsy. The changes in biochemical and lipid profile with KD were also assessed. METHODS: Children aged 6 months to 5 years who had daily seizures (or at least 7 seizures/week) despite the appropriate use of at least three antiepileptic drugs were enrolled. KD was introduced using a non-fasting gradual initiation protocol. Seizure frequency, biochemical profile (liver and kidney function tests, fasting lipid profile, and spot urinary calcium-creatinine ratio) and adverse effects were recorded. Patients continuing KD were followed up for a minimum period of 12 months. RESULTS: Twenty-seven children were enrolled. Non-fasting gradual KD initiation was well tolerated. Eighty-eight percent remained on KD at 3 months, 55% remained on KD at 6 months, and 37% remained on it at 1 year. Intention-to-treat analysis revealed that 48% (13 of 27) had >50% reduction in seizures, and four children (15 %) were seizure free at 6 months. At 1 year, 37% had >50% reduction in seizures and five children (18.5%) were seizure free. Adverse effects included constipation (74%), weight loss (14.8%), edema due to hypo-albuminemia (7.4%) and renal stones (3.7%). Biochemical profile did not reveal significant changes over time, except for reduced serum albumin and increased spot urinary calcium-creatinine ratio. CONCLUSION: KD is an effective and well-tolerated treatment option in young Indian children with refractory epilepsy. However, careful ongoing medical supervision is needed.