Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

The Need for Culturally Appropriate Food Allergy Management Strategies: The Indian Milk Ladder.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and, with a few exceptions, presents in the first few months of life. Baked-milk-containing diets are well tolerated in the majority of milk-allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to an infant's diet in small amounts may enhance the outgrowth of their milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. METHODS: We convened an expert group to develop a comprehensive milk ladder based on the calculated milk protein content of Indian foods. To validate the milk ladder, the foods chosen for the ladder were analyzed and the ladder was re-evaluated based on the cooked milk protein content. RESULTS: Combining expert consensus and validation of milk protein content, we created the world's first milk ladder containing Indian foods. This is the first ladder that provides information on the timing and temperature of cooking, with validated milk protein content. CONCLUSIONS: This is the first milk ladder based on the unique features of Indian food habits built by the consensus of Indian experts along with international collaboration with laboratory quantification of milk protein in each step. We believe the "The Indian Milk Ladder" will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India, but in countries world-wide where these foods are commonly consumed.

Indian Academy of Pediatrics Consensus Guidelines for Probiotic Use in Childhood Diarrhea.

JUSTIFICATION: Several probiotic species and strains, single or combined, have been evaluated in childhood diarrheal disorders, and recommendations have ever been changing as newer trials are published. Therefore, there is a need to develop a guideline for Indian children describing the current role of probiotics in clinical practice. OBJECTIVES: To develop a guideline for the use of probiotics in children with diarrhea. PROCESS: A national consultative group (NCG) was constituted by the Indian Academy of Pediatrics (IAP), consisting of subjects experts. Sub-topics were allotted to various experts as paired groups for detailed review. Members reviewed the international and Indian literature for existing guidelines, systematic reviews, meta-analyses and trials. Thereafter, two virtual structured meetings of the group were held on 2nd and 22nd August, 2020. The management guidelines were formulated by the group and circulated to the participants for comments. The final guidelines were approved by all experts, and adopted by the IAP executive board. RECOMMENDATIONS: The NCG suggests Lactobacillus GG as a conditional recommendation with low-to-moderate level evidence or Saccharomyces boulardii as a conditional recommendation with very low-to-low level evidence as adjuvant therapy in acute diarrhea. The NCG also recommends the use of combination probiotics in neonatal necrotizing enterocolitis (NEC), as these reduce the risk of NEC stage II and above, late-onset sepsis, mortality and also time to achieve full feeds. The NCG does not recommend the use of any kind of probiotics in the therapy of acute dysentery, persistent diarrhea, Clostridium difficile diarrhea and chronic diarrheal conditions such as celiac disease, diarrhea-predominant irritable bowel syndrome and inflammatory bowel disease in children. Risk of antibiotic-associated diarrhea (AAD) is high with some antibiotics and most of these cases present as mild diarrhea. The NCG recommends probiotics only in special situations of AAD. L. rhamnoses GG or S. boulardii may be used for the prevention of AAD. VSL#3, a combination probiotic, may be used as an adjuvant in active pouchitis, prevention of recurrences and maintenance of remission in pouchitis.

Percutaneous Recanalization of Anastomotic Portal Vein in a Pediatric Patient After Liver Transplant Without Any Recognizable Portal Vein Remnant on Imaging.

In patients with complete portal vein thrombosis, the main portal vein is obstructed, resulting in development of hepatopetal collateral vessels. In cases of complete portal vein thrombosis, interventional procedures are challenging, with the greatest difficulty in the form of passing the guide wire across the level of obstruction. A recognizable main portal vein remnant has been deemed as a mandatory criterion in previous reports. Here, we report a case of cavernous trans-formation of the portal vein in a pediatric patient after liver transplant who had no obvious detectable portal vein remnant on radiologic imaging. Using digital subtraction angiography, we were successful in passing a guide wire through the level of obstruction and placing a stent, thus causing successful recanalization of the occluded segment.

Hepatic Visceral Larva Migrans Causing Hepatic Venous Thrombosis and Prolonged Fever.

BACKGROUND: Visceral larva migrans may present with systemic symptoms such as fever, hepatomegaly, pneumonitis or ocular symptoms. CASE CHARACTERISTICS: A 7-year-old girl with fever, pain abdomen and persistent eosinophilia. Imaging and histopathology were suggestive of visceral larva migrans. MESSAGE: The diagnosis of visceral larva migrans is often delayed since similar symptoms of fever, hepatomegaly and peripheral eosinophilia occur in more common and identifiable tropical parasitic and non-parasitic diseases.

Rapunzel syndrome in a seven year old female.

Rapunzel syndrome is characterized by gastric trichobezoar with extension beyond pylorus. Seven year old female presented with chronic pain abdomen and loss of appetite. Upper gastrointestinal (UGI) endoscopy showed large trichobezoar in the stomach with its tail extending into proximal duodenum. Child underwent exploratory laparotomy and a large trichobezoar measuring 15 cm was removed. Psychiatric opinion revealed that the child was suffering from `trichotillomania`; an obsessive compulsive disorder. UGI endoscopy is the preferred modality for diagnosis, as it delineates the mass and its extent. Small bezoars can be extracted via endoscopy using various disintegrating techniques but large bezoars need surgical management.

Infantile Achalasia Cardia.

BACKGROUND: Achalasia is extremely rare in infants. CASE CHARACTERISTICS: We report three infants of age 9, 7 and 12 months, who presented with recurrent non-bilious vomiting, repeated chest infection and severe failure to thrive. Diagnosis of achalasia cardia was confirmed on contrast-swallow study. Hellers cardiomyotomy with fundoplication led to complete symptomatic relief, and weight-gain on follow-up. MESSAGE: Achalasia cardia is often misdiagnosed as gastroesophageal reflux disease which leads to significant delay in diagnosis and increased morbidity.

Fanconi-Bickel syndrome - mutation in SLC2A2 gene.

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism. The defect in the GLUT 2 receptors in the hepatocytes, pancreas and renal tubules leads to symptoms secondary to glycogen storage, glucose metabolism and renal tubular dysfunction. Derangement in glucose metabolism is classical with fasting hypoglycemia and post-prandial hyperglycemia. The authors report a 4-year-old boy who presented with failure to thrive, motor delay, protuberant abdomen and was noted to have huge hepatomegaly with glycogen deposition in liver, and renal tubular acidosis. Gene sequencing revealed homozygous mutation, c.1330T > C in SLC2A2 gene, thus confirming the diagnosis of FBS. Only three mutations have been reported from India so far. The primary reason for referral to authors' hospital was for liver transplantation, but an accurate diagnosis led to avoidance of the major surgery and streamlining of treatment with clinical benefit to the child and family.

Therapeutic interventions in progressive familial intrahepatic cholestasis: experience from a tertiary care centre in north India.

Medical therapy has limited value in managing symptoms of progressive familial intrahepatic cholestasis (PFIC). Liver transplantation (LT) is the only definite therapy for progressive liver failure and intractable pruritis. In recent years, biliary diversion (BD) has also shown therapeutic promise. This study was designed to review the experience of management and outcome of seven PFIC patients. Two children each had type II and III and three had type I/II PFIC, respectively. Medical treatment was successful in only one. Decompensated cirrhosis had already set in four children. They underwent a living related LT. There was one post transplant mortality. Remaining all children had a normal graft function at a mean follow-up of 50 months. One patient of PFIC type I/II received internal and another of PFIC type II received external BD. Both patients were asymptomatic at follow-up of 19 and 23 months respectively. Nontransplant surgical options should be offered to noncirrhotic children with PFIC.

Outcome of live donor liver transplantation in Indian children with bodyweight <7.5 kg.

This case-series analyzed the outcome of live donor liver transplantation (LT) performed in children <7.5 kg from January 2008 to June 2009 at our center. Five patients (3 males, 2 females, mean age, 8.2 ± .4 months; mean weight 6.8 ± 0.4 kg) underwent LT. The indications of LT included biliary atresia (3) and idiopathic neonatal hepatitis (2). Postoperative complications included acute rejection (1), portal venous thrombosis (1), bile leak (1), severe hypertension (1) and bacterial sepsis (4). There were no donor related complications. The median follow-up duration is 11 months with patient and graft survival rates of 100% each, respectively.