Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature.

A 3-year-old boy, firstborn to nonconsanguineous parents, presented with motor development delay and floppiness of bilateral lower limbs since birth. No significant family history presented at time of check-up. He could stand with support, eat with a spoon without spillage, and speak in two-word sentences. There was no history suggestive of cranial nerve impairment. Examination revealed normal head circumference, dry, scaly skin lesions on the trunk, distal weakness with sluggish deep tendon reflexes in bilateral lower limbs, and a high stepping gait. Nerve conduction studies revealed demyelinating polyneuropathy. Brain stem-evoked response audiometry testing revealed auditory neuropathy. Clinical exome sequencing revealed a known pathogenic variant of 3325C > T in the SH3TC2 gene suggestive of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with a novel variant of 2218C > T in the FLG gene. We have reviewed the available literature for reported associations of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris. This is probably the first reported association of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with bilateral hearing loss.

Burden of Attention Deficit Hyperactivity Disorder (ADHD) in Indian Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the pooled prevalence of attention deficit hyperactivity disorder (ADHD) in Indian children. METHODS: The searching of published literature was conducted in different databases (PubMed, Ovid SP, and EMBASE). The authors also tried to acquire information from the unpublished literature about the prevalence of ADHD. A screening was done to include eligible original studies, community or school-based, cross-sectional or cohort, reporting the prevalence of ADHD in children aged ≤ 18 y in India. Retrieved data were analyzed using STATA MP12 (Texas College station). RESULTS: Of 729 studies retrieved by searching different databases, 183 studies were removed as duplicates, and 546 titles and abstracts were screened. After screening, 19 studies were included for quantitative analysis. Subgroup analysis was conducted with respect to their setting (school-based/community-based). Fifteen studies performed in a school-based setting showed 75.1 (95% CI 56.0-94.1) pooled prevalence of ADHD per 1000 children of 4-19 y of age. In community-based settings, the pooled prevalence per 1000 children surveyed was 18.6 (95% CI 8.8-28.4). The overall pooled prevalence of ADHD was observed as 63.2 (95% CI 49.2-77.1) in 1000 children surveyed. Significant heterogeneity was observed in the systemic review. CONCLUSIONS: ADHD accounts for a significant health burden, and understanding its burden is crucial for effective health policy-making for educational intervention and rehabilitation.

Financial Burden in Families of Children with West Syndrome.

OBJECTIVE: To evaluate the illness-related expenditure by families of children with West syndrome (WS) during the first year of illness and to explore the potential determinants of the financial drain. METHODS: This cross-sectional study was conducted at a tertiary care hospital between July 2018 and June 2020. Eighty-five children with WS who presented within one year from the onset of epileptic spasms were included. The details of the treatment costs (direct medical and nonmedical) incurred during the first year from the onset of epileptic spasms were noted from a parental interview and case record review. Unit cost was fixed for drugs and specific services. Total cost was estimated by multiplying the unit cost by the number of times a drug or service was availed. The determinants of the financial burden were also explored. RESULTS: The median monthly per-capita income of the enrolled families (n = 85) was INR 3000 (Q1, Q3, 2000, 6000). The median cost of treatment over one year was INR 27035 (Q1, Q3, 17,894, 39,591). Median direct medical and nonmedical expenses amounted to INR 18802 (Q1, Q3, 12,179, 25,580) and INR 6550 (Q1, Q3, 3500, 15,000), respectively. Seven families had catastrophic healthcare expenditure. Parental education and choice of first-line treatment were important determinants driving healthcare expenses. The age at onset of epileptic spasms, etiology, treatment lag, the initial response to treatment, and relapse following initial response did not significantly influence the illness-related expenditure by the families. CONCLUSION: WS imposes a substantial financial burden on the families and indirectly on the healthcare system.

Prospective Cohort Study on Cumulative Fluid Balance and Outcome in Critically Ill Children Using a Restrictive Fluid Protocol.

OBJECTIVE: To study the association of cumulative fluid balance and clinical outcomes in a pediatric intensive care unit (PICU) practicing restrictive fluid protocol. METHODS: In this prospective cohort study, children aged less than 13 y admitted for more than 48 h were screened. Children with unstable hemodynamics throughout the stay were excluded. Fluid balance was calculated by percentage fluid overload (%FO) for the first 7 d. Patients were divided into positive fluid and negative fluid balance groups. The primary outcome was all-cause 28-d mortality. RESULTS: A total of 888 patients (positive fluid balance group = 531, negative fluid balance group = 357) were analyzed. Mean (SD) cumulative %FO was 1.52 (0.67) vs. -1.18 (0.71), p = < 0.001, and minimum and maximum cumulative %FO were -3.0% and 3.1%, respectively. There was no significant difference in all-cause 28-d mortality between the two groups (n = 104/531, 19.6% vs. n = 60/357, 16.8%, RR = 1.17, 95% CI 0.87 to 1.55; p = 0.29). There was no difference in organ dysfunction [mean (SD) sequential organ failure assessment (SOFA) score 3.3 (0.7) vs. 3.3 (0.6)], acute kidney injury (65% vs. 63.6%), need for renal replacement therapy (14% vs. 13%), and duration of ventilation (median, IQR 4, 2-6 vs. 4, 2-6 d). Longer stay in PICU (5, 3-9 vs. 4, 3-7 d; p = 0.014) and in hospital (8, 5-11 vs. 7, 4-10 d; p = 0.007) were noted in the positive fluid balance group. CONCLUSION: Cumulative fluid balance within 3% using restrictive fluid protocol was not associated with a significant difference in PICU mortality and morbidity.

Prospective Inverse Probability of Treatment-Weighting Analysis of the Clinical Outcome of Red Blood Cell Transfusion Practice in Critically Ill Children.

OBJECTIVE: To study the clinical outcomes of red blood cell (RBC) transfusion practices in critically ill children. METHOD: This prospective cohort study was conducted in a tertiary care pediatric intensive care unit (PICU) from March-2015 to January-2018. Inverse probability of treatment weighting (IPTW) using propensity score analysis was used. Children aged 1 mo to 12 y admitted to the PICU were screened. Patients were classified into 'transfused' and 'nontransfused', based on whether they received a transfusion or not. Patients with hematological malignancies, or immunosuppressant drugs, or those who received repeated transfusions, or received transfusion before admission, or died within 24 h were excluded. The primary outcome was all-cause 28 d mortality. Secondary outcomes were new-onset organ dysfunction, mechanical ventilation duration, and length of PICU and hospital stay. RESULTS: A total of 1014 patients [transfused = 277; nontransfused = 737) were included. In IPTW analysis, the risk of all-cause 28 d mortality was 53% higher in transfused than nontransfused patients [hazard ratio = 1.53, 95% CI: 1.18-1.98, p = 0.001 by Log-rank test]. Organ dysfunction was higher in transfused than nontransfused patients [3.8% vs. 1.3%, hazard ratio = 3.0, 95% CI: 1.40-6.48, p = 0.005]. The risk of staying in the mechanical ventilation was similar in both groups [hazard ratio = 1.03, 95% CI: 0.86-1.23, p = 0.756]. The risk of extended stay in the PICU and hospital was 16% and 21% higher in transfused than nontransfused patients [hazard ratio = 1.16, 95% CI: 1.03-1.30; p = 0.005; and 1.21, 95% CI: 1.08-1.36; p = 0.001], respectively. CONCLUSION: Red blood cell transfusion was independently associated with higher all-cause 28 d mortality and morbidities in critically ill children.

Long-term epilepsy control, motor function, cognition, sleep and quality of life in children with West syndrome.

PURPOSE: To assess epilepsy, motor function, cognitive, sleep, and quality of life outcomes and their predictors in a follow-up cohort with West syndrome (WS) at ≥5 years of age. METHODS: Cross-sectional evaluation in a follow-up cohort of WS (aged 5-14 years), between July 2018 and December 2019, was performed at a tertiary-care referral center in Northern India. 164 children were assessed in-person for epilepsy severity, functional status (gross motor and hand function), social quotient, behavioral comorbidities, sleep problems, and quality of life (QoL) using Early Childhood Epilepsy Severity Scale, Gross Motor Function Classification System, Manual Ability Classification System, Vineland Social Maturity Scale, Diagnostic and Statistical Manual of Mental disorders-5 criteria, Children's Sleep Habits Questionnaire, and PedsQL-Epilepsy module respectively. Furthermore, 238 children with the inability to visit the hospital were assessed through telephonic interview along with retrospective case record review for epilepsy control, gross and fine motor measures. RESULTS: 402 children with WS (75 % boys) with regular follow-up were studied and the majority (80 %) had underlying structural etiology. The median age (interquartile range) of the cohort was 92 (78-107) months. Of these, 60 % had evolved to Lennox-Gastaut syndrome (LGS). The following long-term outcomes were observed: ongoing epilepsy (261/402), unfavorable motor status (130/402), moderate to profound intellectual disability (111/164), autistic spectrum disorder (42/164), attention-deficit hyperactivity disorder (18/164), poor sleep (135/164), and impaired QoL (115/164). Non-structural etiology (odds ratio [OR] = 3.8, 95 % confidence interval [CI]: 2.1-5.5, p=<0·0001) and older age (>5 months) at the onset of epileptic spasms (OR = 2·9, 95 % CI: 1.5-5.0, p=<0·0001) were associated with enduring seizure freedom for more than two years. CONCLUSION: The present study revealed a preponderance of structural etiology and a high rate of transition to LGS. Early age at onset of spasms (before five months) and structural etiology were the predictors of unfavorable long-term epilepsy outcome. QoL was impaired in more than two-thirds of patients and it correlated significantly with cognitive, sleep, motor, and behavioral outcomes. However, the results of our study should be interpreted in the context of significant attrition of the original cohort.

Levamisole in Frequently-relapsing and Steroid-dependent Nephrotic Syndrome.

OBJECTIVE: To evaluate the efficacy of levamisole in children with frequently relapsing nephrotic syndrome (FRNS) and steroid dependent nephrotic syndrome (SDNS) when administered on an alternate day ('initial therapy' in all cases) or daily basis ('rescue therapy' in whom alternate day therapy failed). METHODS: The records of 95 children (age 1-18y) with FRNS (62) and SDNS (33), who were treated at the Pediatric nephrology clinic, and received levamisole therapy (maximum 2 y duration, between 2010-2013) with a follow-up period of minimum 1 y, were included. RESULTS: Alternate day levamisole therapy was efficacious in 73.7% (n=70). The overall efficacy of levamisole therapy was 88.4% (n=84). Levamisole therapy decreased the mean (SD) number of relapses from 4.22 (0.46)/y to 1.35 (0.36)/y (P<0.01); and cumulative median (IQR) prednisolone dosage from 4200 (3200-4300) mg/m2 to 1100 (IQR 500-2900) mg/m2 (P<0.001). On a one-year follow up of the cases in whom levamisole therapy was efficacious during therapy (median 24 mo) (n=84), a frequently relapsing or steroid dependent course continued to persist in 48.8% (41), necessitating oral cyclophosphamide (n= 22) or mycophenolate mofetil (n=19). CONCLUSION: Daily levamisole therapy was useful in 56% of children who demonstrated failure while on alternate day levamisole therapy, and could be a useful therapeutic option in FRNS and SDNS.