Mevalonate Kinase Deficiency as Cause of Periodic Fever in Two Siblings

Mevalonate kinase deficiency (MKD) is a rare autosomalrecessive autoinflammatory disease caused by mutations inMVK. We report two siblings with MKD, presenting withrecurrent febrile illnesses, detected to have compoundheterozygous variants in MVK. MKD mimics common pediatricconditions and should be considered as a differential diagnosis.

Hepatitis A Virus-related Pediatric Liver Disease Burden and its Significance in the Indian Subcontinent

Objectives: To study the Hepatitis A virus (HAV) infection-related pediatric liver diseaseburden. Methods: Hospitalrecords of 431 children (age <18 y) diagnosed to be sufferingfrom acute HAV infection during 2011 to 2018 were extracted and analyzed. Additionally, aseroprevalence study was done on 2599 participants (696 children and 1903 adults).Results: HAV infection accounted for about half (48.6% of acute hepatitis and 46.5% (92/198) of acute liver failure cases) of all acute onset icteric illness, with significant morbidity andmortality. As per seroprevalence data, 16.2% of children between 10-18 years of age, and10.3% of adults aged 18-30 years remained susceptible to HAV infection. Conclusion: HAVinfection is the major contributor the overall pediatric liver disease burden. A significantproportion of subjects remain susceptible to HAV infection even after 10 years of age.Population-based studies are required to further delineate the epidemiology of HAV infectionin India for deciding introduction of HAV vaccine in the national immunization schedule.

Study of Family Clustering and PNPLA3 Gene Polymorphism in Pediatric Non Alcoholic Fatty Liver Disease

Objectives: To find association of pediatric NAFLD with metabolicrisk factors, and Patatin-like phospholipase domain-containingprotein 3 (PNPLA3) gene polymorphism.Design: Cross-sectional studySetting: Pediatric Hepatology unit of a tertiary care hospitalParticipants: Overweight/obese children (<18 years) with (69patients) or without (30 patients) NAFLD (ultrasonographybased), and their parents.Intervention: Metabolic screening, PNPLA3 gene polymorphism,and transient elastographyOutcome measure: Association of pediatric NAFLD with parentalmetabolic risk factors and PNPLA3 gene polymorphism.Results: In the NAFLD group, there was high parental incidenceof metabolic diseases, fatty liver (80%) and low high-densitylipoproteins levels (84%). Family history of NAFLD (in any parent),higher alanine aminotransferase levels and higher totalcholesterol levels in the child independently predicted possibilityof NAFLD, but similar results could not be replicated for PNPLA3gene polymorphism. Controlled attenuation parametermeasurement (by transient elastography) had high sensitivity andspecificity to diagnose steatosis.Conclusion: There is high familial incidence of metabolicdiseases in children with NAFLD. Controlled attenuationparameter can be useful as a non-invasive modality to screen fattyliver in children.

Metabolic Liver Diseases Presenting as Acute Liver Failure in Children.

Context: Suspecting metabolic liver disease in an infant or young child with acute liver failure, and a protocol-based workup for diagnosis is the need of the hour. Evidence acquisition: Data over the last 15 years was searched through Pubmed using the keywords "Metabolic liver disease" and "Acute liver failure" with emphasis on Indian perspective. Those published in English language where full text was retrievable were included for this review. Results: Metabolic liver diseases account for 13-43% cases of acute liver failure in infants and young children. Etiology remains indeterminate in very few cases of liver failure in studies where metabolic liver diseases were recognized in large proportion. Galactosemia, tyrosinemia and mitochondrial disorders in young children and Wilson’s disease in older children are commonly implicated. A high index of suspicion for metabolic liver diseases should be kept when there is strong family history of consanguinity, recurrent abortions or sibling deaths; and history of recurrent diarrhea, vomiting, failure to thrive or developmental delay. Simple dietary modifications and/or specific management can be life-saving if instituted promptly. Conclusion: A high index of suspicion in presence of red flag symptoms and signs, and a protocol-based approach helps in timely diagnosis and prompt administration of life-saving therapy.

Reverse Vertical Transmission of Hepatitis-B from Transfusion-infected Children to Biological Mothers.

Background: Perinatal and horizontal are the common modes of transmission of hepatitis-B virus in children. Case characteristics: Two mother-child pairs with children having received multiple blood transfusions in past. Observation: Both the mothers developed acute hepatitis-B infection whereas children were demonstrated to be having chronic infection with hepatitis-B. Outcome: One mother cleared her hepatitis-B in fection whereas it persisted in the other. Both children required anti-viral treatment. Message: Hepatitis-B virus may rarely get transmitted from infected children to their mothers causing acute infection.

Determinants of Vitamin A Deficiency amongst Children in Aligarh District, Uttar Pradesh.

Objectives: To determine the prevalence and determinants of xerophthalmia among children aged 0-60 months . Methods: This cross-sectional study included 3571 children under 5 years of age from six villages and four periurban areas. Children with xerophthalmia were identified and severity graded using the WHO classification. The main outcome measures were sociodemographic, nutritional and comorbidity related risk factors of xerophthalmia. A pretested questionnaire carrying information on the above factors was administered to the caregivers. Univariate and multivariate binary logistic regression analyses were performed to examine the association of each of these factors with xerophthalmia. Results: The overall prevalence of xerophthalmia was of serious public health importance at 9.1%. Prevalence of both mild (night blindness, and Bitot’s spots) and severe forms (corneal changes) of xerophthalmia increased with age. Bitot’s spots and night blindness were the commonest manifestations. Rural dwelling, lower social class, maternal illiteracy and occupation outside home were significant antecedent socio-demographic risk factors on univariate analysis. Multivariate analysis revealed low intake of proteins and vitamin A containing foods as well as predominant maize diet to be significant dietary factors. Nutritional wasting and a preceding history of measles were significant comorbid determinants (P<0.05). None of the socio-demographic variables emerged significant on multivariate analysis. Conclusions: Vitamin A deficiency remains a significant public health problem in Aligarh district.The proximal factors in a child’s mileu viz nutrition and comorbidities were more significantly associated with xerophthalmia than the distal socio-demographic factors, thereby making a case for their cost effective prevention.The high magnitude of the problem calls for intensification of existing prophylactic measures in these areas.

Global developmental delay and its determinants among urban infants and toddlers: A cross sectional study.

Objective To estimate the prevalence of global developmental delay among children under 3 years of age and study the determinant factors. Methods Cross sectional descriptive study was conducted in field practice areas of the Department of Community Medicine, JN Medical College, Aligarh, India. A total of 468 (243 boys and 225 girls) children aged 0–3 years were included. Developmental screening was performed for each child. A multitude of biological and environmental factors were analysed. Results As many as 7.1% of the children screened positive for global developmental delay. Maximum delay was observed in the 0–12 months age group (7.0%). Undernutrition and prematurity were the two most prevalent etiological diagnoses (21% each). Stunting and maternal illiteracy were the microenvironmental predictors on stepwise binary logistic regression while prematurity and a history of seizures emerged significant biological predictors. Conclusions Developmental delay can be predicted by specific biological and environmental factors which would help in initiating appropriate interventions.

Screening children with severe short stature for celiac disease using tissue transglutaminase.

Objective. To determine the prevalence of anti-tissue transglutaminase in children and adolescents with severe short stature (<-3 SD). Methods. All children in age group of 1-18 years having height less than -3 SD for their age and sex, were included. For each child age and sex matched healthy control (height more than -2 SD) was taken. The included subjects (study & control group) were subjected to anti tissue transglutaminase (tTG) (IgA) antibody assay estimation. Results. Of the 112 cases, 23 were tTG positive, giving a prevalence of 20.5% for seropositivity among cases of short stature while all the controls were seronegative for tTG. All the 23 had tTG values above 40 U/ml and 11 had values above 100 U/ ml. On univariate analysis we found that the presence of chronic diarrhea (OR = 2.55, 95%CI - 1.08-5.98), bulky stools (OR = 3.03, 95%CI - 1.52-6.05), hemoglobin < 7 gm/dl (OR = 3.12, 95%CI - 1.55 - 6.29) and more severe short stature (<-4 SD) (OR = 0.41, 95%CI - 0.17- 0.95) had significant association with the tTG positivity. On logistic regression analysis in all cases, hemoglobin < 7gm/dl (OR = 0.090, 95%CI = 0.024-0.342) and bulky stools (OR=0.212, 95%CI = 0.069-0.649) were significantly associated with tTG positivity. Conclusion. More than one fifth of all severe short stature are seropositive for tTG and the chances of seropositivity increases if severe anemia and bulky stool are also associated.

Antibiotic associated diarrhea in children.

Context: Keeping in view the recent flooding of the Indian market with antibiotic and probiotic combinations, we decided to look at the prevalence of antibiotic associated diarrhea (AAD) and Clostridium difficile infection (CDI) in children and reviewed evidence available for use of probiotics in the prevention of AAD. Evidence acquisition: We did a PubMed, Medline and Cochrane libary search for literature available in last 25 years. Results: Prevalence of antibiotic associated diarrhea (AAD) is around 11%. Children younger than 2 years and type of antibiotics are the two risk factors identified for AAD. For the pediatric population, CDI reportedly decreased in a tertiary care hospital in India, though number of suspected samples tested increased. The incidence of community acquired CDI is increasing in the pediatric population also. Detection of toxin A and B by enzyme linked immunosorbent assay (ELISA) and detection of toxin B by tissue culture form the mainstay in the diagnosis of C. difficile. Most of the AAD would respond to only discontinuation or change of the antibiotic. Oral metronidazole or oral vancomycin are drugs of choice for CDI. Probiotics reduce the risk of AAD in children and for every 7-10 patients one less would develop AAD. Conclusion: Prevalence of AAD is low and majority will respond to discontinuation of antibiotic. CDI is uncommon in children. Probiotics will prevent AAD in only 1 in 7 children on antibiotics. We need cost effectiveness studies to decide the issue of needing a probiotic antibiotic combination to prevent AAD.

Current status of anti-diarrheal and anti-secretory drugs in the management of acute childhood diarrhea.

Each year 1.8 million children die due to diarrheal diseases. Indiscriminate use of antibiotics has resulted in increasing resistance to commonly used antibiotics. Moreover the recent outbreaks of shigella and cholera have revealed multi-drug resistance strains. There is a need for review of recommended antibiotics for shigellosis. From recent data it emerges that fluoroquinolones should be the first line of therapy and cephalosporins to be used as the second line. Among the anti-cholera antibiotics, tetracyclines which were the drug of choice for adults, has the advantage of high sensitivity and low cost. Single dose doxycycline would have minimal side effects, hence can be the drug of choice even in children. We should not allow the business pressures to force usage of probiotics and racecadotril as their role in the management of acute diarrhea is yet to be established. Nitazoxanide has high efficacy against Cryptosporodial diarrhea only. Strict adherence to the recommendations for the management of acute childhood diarrhea is needed or else we dilute the effect of standard management.

Alpha-1 antitrypsin deficiency among Indian children with liver disorders.

AIMS: To determine the frequency of alpha-1 antitrypsin (AAT) deficiency in children with chronic liver disease (CLD) and neonatal cholestasis syndrome (NCS). METHODS: All children with NCS (n=23) or CLD (n=35) attending the Pediatric Gastroenterology Clinic between November 2003 and July 2005 were screened for AAT deficiency using phenotyping through isoelectric focusing of plasma. RESULTS: Of the 58 children studied, 57 had normal PiMM phenotype. One child with CLD had the M1E type of normal variant. None of the patients had the abnormal phenotype PiZZ. CONCLUSION: AAT deficiency is infrequent among children with CLD and NCS in our region.

Efficacy of tyndalized Lactobacillus acidophilus in acute diarrhea.

OBJECTIVE: A double-blind randomized controlled-trial was done to evaluate the efficacy of tyndalized Lactobacillus acidophilus in acute diarrhea. METHODS: All children from 6 months to 12 years with acute diarrhea were included. Lactobacillus acidophilus/placebo was given to the children for 3 days with ORS and feeds. Intake-output was recorded 4 hourly. Of the 98 children, 48 received lactobacillus and 50 the placebo. RESULTS: ORS consumed, frequency of stools, duration of diarrhea, time for rehydration, hospital stay, weight gain and IVF needed were comparable in the two study groups. There were 4 treatment failures in the lactobacillus group and none in the placebo group (OR 0.92, 95%CI 0.84-0.99). In the rotaviral diarrhea and in those who had diarrhea of less then 60 hours the difference did not reach statistical significance. CONCLUSION: There is no significant benefit of tyndalized Lactobacillus acidophilus in acute diarrhea.

Age-specific prevalence of hepatitis B surface antigen in pediatric population of Aligarh, North India.

OBJECTIVE: To estimate the age-specific seroprevalence of hepatitis B surface antigen (HBsAg) in children upto 14 years of age. METHODS: Equal number (115 each) of apparently healthy children of both sexes of different age groups i.e. < 1, 1-4, 5-9 and 10-14 years, attending pediatric outpatient services and Well Baby Clinic of the hospital were tested for HBsAg using ELISA test. Positive results were confirmed by a second ELISA. RESULTS: Overall 4.35% (95%CI, 2.44 - 6.25) of the 460 children tested were HBsAg positive. The prevalence rate was the highest (6.09%) in the 1-4 year age category. In the < 1, 5-9 and 10-14 year age groups it was 4.35%, 4.35% and 2.61% respectively. The overall male to female ratio was 2.1:1, with no significant difference in seropositivity rates (P = 0.816).The difference in the prevalence rates between the rural (4.84%) and urban populations (3.77%) was also statistically insignificant (P = 0.577). CONCLUSION: Average HBsAg positivity in the pediatric population in this region is 4.35% (95%CI, 2.44 - 6.25). The prevalence progressively increases and peaks in the 1- 4 years age group. It is least in 10-14 years age group.

Knowledge of diarrhea management among rural practitioners.

OBJECTIVE: To determine diarrhea management in rural practitioners. METHODS: This study was conducted among the RMP's of 4 blocks of Aligarh. Pre-coded questionnaire was completed and educational programme followed. 91% were prescribing ORS in various combinations, but only 9.8% were advising ORS and feeding as standard management of diarrhea. Only 12.8% could name a WHO ORS brand and 50% were giving wrong instructions for preparation. 95% were advising inadequate amounts of ORS. Only 43.5% were advising feeding during diarrhea but 86.6% were advising to continue breastfeeding. On an average every 3rd to 4th patient was administered IVF's. 52% felt that drugs should be prescribed. RESULTS: 90% and 55.3% of RMPs could identify diarrhea and key signs of dehydration. CONCLUSION: There is a need for hands on training for the practitioners and education of the masses regarding proper management of diarrhea.