CASE: Here we describe three infants with TNMG. Two of them developed symptoms of TNMG within 24 hours of life, but one developed symptoms at 43 hours of life. One of the patients had an atypical form of TNMG with contracture and hypotonia. The other two infants survived a typical form of TNMG with hypotonia and poor sucking. All cases resolved spontaneously by one to two weeks of life with conservative management.

CASE DESCRIPTION: We report on a paediatric case of pleural TB complicated with complex chylothorax, and systematically reviewing the literature for cases of tuberculous chylothorax among children particularly looking at the (I) demographic, (II) clinical presentations, (III) radiological findings, and (IV) investigations among this cohort of patients. The systematic review complied to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used three separate databases, namely PubMed, Ovid, and Scopus to search for articles with terms "chylothorax", "tuberculosis", and "children". We included article reporting on: (I) children aged below 18; (II) infected by Mycobacterium TB, and (III) written in English only. We reviewed the publications from the inception up to August 2022. After an extensive search, 7 articles were reviewed. We included 10 patients from all the reports. Most common symptoms reported were intermittent fever (n=6) and chronic cough (n=5). Other symptoms include shortness of breath and chest discomfort due to fluid accumulation and/or effusion. Typical TB symptoms like night sweat, loss of weight, and loss of appetite were present in some of the reported patients. Chest radiography was the most used diagnostic imaging modality, in which all of the reported cases noted presence of pleural effusion, with some cases proceeded with computer tomography (CT) of thorax to aid in the diagnosis. Most of the patients had lymphadenopathies and all patients underwent pleural tapping for analysis and symptomatic relief. From the pleural fluid milky appearance and biochemistry correlation, the diagnosis of chylothorax was established in all 10 patients. Every patient was tested positive for TB infection.

METHODS: A total of 149 patients were included in the study. HBA and HBB mutations were characterised using multiplex PCR, Sanger sequencing and multiplex ligationdependent probe amplification. In addition, 35 HbF polymorphisms were genotyped using mass spectrometry and PCR-restriction fragment length polymorphism (PCRRFLP). The genotype-phenotype association was analysed using SPSS version 22.

RESULTS: Twenty-one HBB mutations were identified in the study population. Patients with HBB mutations had heterogeneous phenotypic severity due to the presence of other secondary modifiers. Co-inheritance of α-thalassemia (n = 12) alleviated disease severity of β-thalassemia. In addition, three polymorphisms (HBS1LMYB, rs4895441 [P = 0.008, odds ratio (OR) = 0.38 (0.18, 0.78)], rs9376092 [P = 0.030, OR = 0.36 (0.14, 0.90)]; and olfactory receptor [OR51B2] rs6578605 [P = 0.018, OR = 0.52 (0.31, 0.89)]) were associated with phenotypic severity. Secondary analysis of the association between single-nucleotide polymorphisms with HbF levels revealed three nominally significant SNPs: rs6934903, rs9376095 and rs9494149 in HBS1L-MYB.

METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored.

RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045).

CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children.