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.

Intractable diarrhea in an infant-autoimmune enteropathy: A case report.

Autoimmune enteropathy is a rare cause of chronic intractable diarrhea and is present in <1 in 100,000 infants. We report the case of a 9-month-old boy who presented with intractable diarrhea and vomiting. Genetic panel testing revealed a STAT3 heterozygous mutation in exon 6, suggesting infantile-onset multisystem autoimmune disease-1. The patient was initially treated with steroids and sulfasalazine. However, on tapering steroids, he had another episode of diarrhea and was subsequently put on baricitinib to which he responded.

Difficult to treat liver abscesses in children - Do not forget parasitic infections.

Liver abscess (LA) is a significant health concern worldwide, particularly in tropical regions such as India, and is usually pyogenic or amoebic in origin. In rare cases it can be caused by parasites. We present two children with difficult-to-treat LAs, revealing underlying parasitic infections as the causative agents, implicated by eosinophilia, elevated immunoglobulin-E levels and exposure to domestic animals. In the first case, disseminated echinococcosis was diagnosed through imaging, serology and histopathology. The second case showed a relationship between LAs and Toxocara infection, evidenced by microscopic stool examination of a household cat.

Endoscopic balloon dilation of esophageal stricture in dystrophic epidermolysis bullosa patient: challenges faced and safety of procedure.

BACKGROUND: Epidermolysis Bullosa (EB) stands as the prototype category of disorders featuring subepidermal fragility, characterized by skin blistering induced by minimal trauma. The gastrointestinal tract is a common site of extracutaneous injury. Esophageal stricture (ES) is one of the severe complications, with nearly 70% of patients experiencing ES within the initial 25 years of life. CASE REPORT: We present a 11-year-old female child of dystrophic EB (DEB) who presented with dysphagia. Barium swallow showed a short segment proximal ES. We faced many challenges before endoscopy owing to difficult intravenous access, restricted mouth opening, multiple dental caries and low haemoglobin. Dental extraction under general anaesthesia and fibreoptic intubation with a smaller sized endotracheal tube guided over epidural catheter was done at another tertiary care institute. Child had severe bleeding due to airway manipulation. MANAGEMENT: At our centre endoscopy guided serial balloon dilation (BD) of ES was performed without intubation under total intravenous anaesthesia (TIVA) without any complications. The stricture was serially dilated under direct visualization till 12 mm in three sessions at three-weekly intervals using CRE (controlled radial expansion) fixed and wire-guided balloon dilators. During the first session 20 mg of triamcinolone acetate injection was also topically applied without mucosal invasion. No such further topical or submucosal applications were attempted due to risk of perforation. CONCLUSION: Endoscopy guided BD of ES is safe and effective in EB patients when done by experienced team.

Diagnosis and Management of Infections in Patients with Mendelian Susceptibility to Mycobacterial Disease.

The diagnosis and treatment of patients with mendelian susceptibility to mycobacterial disease (MSMD) pose consistent challenges due to the diverse infection spectrum observed in this population. Common clinical manifestations include Bacillus Calmette-Guérin vaccine (BCG) complications in countries where routine BCG vaccination is practiced, while in non-BCG-vaccinating countries, Non-Tuberculous Mycobacteria (NTM) is prevalent. In tuberculosis-endemic regions, Mycobacterium tuberculosis (MTB) has a high prevalence, along with other intracellular organisms. Isolating these organisms presents a significant challenge, and treatment is often initiated without confirming the specific species. This review primarily focuses on the methods and challenges associated with diagnosing and treating MSMD patients.

Effect of delamanid on interim outcomes of bacteriological conversion amongst pediatric drug resistant tuberculosis cases in India.

AIM: To determine the bacteriological conversion rate after 6 months of Delamanid (DLM) based treatment in children with drug-resistant tuberculosis (DR-TB) and determine factors associated with bacteriological conversion. METHODS: This is a descriptive retrospective study done in children between the age of 6-17 years with DR-TB who received DLM-based therapy from October 2018 to May 2021. The drug resistance pattern of TB was detected using Xpert RIF/MTB and phenotypic drug sensitivity testing (DST) on TB-MGIT culture reports. Follow-up sputum TB MGIT culture was carried out monthly after DLM initiation for 6 months. Factors associated with sputum bacteriological conversion such as age, gender, pulmonary TB (PTB) versus disseminated TB, unilateral or bilateral lung involvement, type of DR-TB, prior treatment failure, and type of DR-TB regimen were analyzed. RESULTS: Sixty patients received DLM of which two had extrapulmonary TB (EPTB) and sputum conversion could not be assessed. The mean age at presentation was 12.69 ± 3.03 years. Five patients (8.3%) died while on DLM treatment. On follow-up, 8 (13.7%) out of 58 patients had no sputum bacteriological conversion after 6 months of DLM initiation of which three patients were on salvage therapy; 46 (79.3%) had sputum bacteriological conversion within 6 months of DLM initiation. CONCLUSION: Sputum bacteriological conversion rate was almost 80% at the end of 6 months of DLM-based treatment.

Latent TB in Indian pediatric population: An update on evidence gaps and research needs.

The main aim of this article is to review various studies conducted in relation to diagnosis, treatment and management of Latent TB Infection (LTBI) in under-five children, thus highlighting research gaps and further scope of improvements with respect to Indian context. The methodology involved literature review of various online review articles and research papers along with current published guidelines for LTBI management by World Health Organization (WHO) and National tuberculosis Elimination Program (NTEP). There is a dearth of statistically significant data regarding prevalence of LTBI among under-five children in India. LTBI prevalence in Indian adults has been reported between 21 and 48%. The exact prevalence of pediatric LTBI in India is still not clear, however, as per few studies, the LTBI prevalence ranges around 40% and 22% in adolescent followed by under-5 population. Studies to fill in the research gap of scarcity of prevalence data, regarding pediatric LTBI in high TB burden areas of India, is a pivotal step to curb the global pandemic of TB disease. There is a massive undervaluation of the true burden of childhood LTBI as the influence of environmental reservoir in childhood LTBI and TB are not accounted for in pediatric LTBI regimens. Also, there is no substantiate amount of data that highlights the other aspects of LTBI in pediatric population, like awareness regarding LTBI condition and other physiological adverse effects of LTBI in pediatric population, which have been often observed in under-five children suffering from LTBI.

Response of HIV-associated proteinuria to antiretroviral therapy in HIV-1-infected children

HIV-associated nephropathy has been found in children with HIV-1 infection as a late manifestation of this disease; it is associated with nephrotic syndrome with focal segmental glomerulosclerosis and/or mesangial hyperplasia with microcystic tubular dilatation. This is quite rare in children and no cases have been reported from India. Several mechanisms have been hypothesized for the HIV-induced renal damage. We report on two HIV-infected children with HIV-associated proteinuria and dramatic response to antiretroviral therapy.