Interventions that encompass behavioural modifications of dietary intake and physical activity are essential for the management of obesity in children. This study assessed the effectiveness of a stage-based lifestyle modification intervention for obese children. A total of 50 obese children (7–11 years old) were randomized to the intervention group (IG, n = 25) or the control group (CG, n = 25). Data were collected at baseline, at follow-up (every month) and at six months after the end of the intervention. IG received stage-based lifestyle modification intervention based on the Nutrition Practice Guideline for the Management of Childhood Obesity, while CG received standard treatment. Changes in body composition, physical activity and dietary intake were examined in both the intervention and control groups. Both groups had significant increases in weight (IG: 1.5 ± 0.5 kg; CG: 3.9 ± 0.6 kg) (p < 0.01) and waist circumference (IG: 0.1 ± 0.5 cm; CG: 2.2 ± 0.7 cm) (p < 0.05), but the increases were significantly higher in CG than IG. Body Mass Index (BMI)-for-age z scores decreased significantly in IG (− 0.2 ± 0.0, p < 0.01) but not in CG. The physical activity of the IG significantly increased (0.44 ± 0.13) compared with that of CG (− 0.28 ± 0.18), and the difference in mean change between groups was statistically significant (p < 0.05). Dietary intake was not significantly different between the two groups. However, calorie and carbohydrate intake decreased significantly in both groups. A stage-based intervention that modified dietary and physical activity behaviour may be effective in weight management for obese children. NCT03429699 retrospectively registered 9 February 2018.

Hypophosphataemic rickets (HR) is a genetic disorder causing defects in the renal handling of phosphorus, resulting in rickets. HR can be classified into two groups. First- those with excess fibroblast growth factor 23(FGF23) levels, which are due to gene mutations in extrarenal factors and include X-linked dominant hypophosphataemic rickets (XLHR), autosomal dominant hypophosphataemic rickets (ADHR), autosomal recessive hypophosphataemic rickets (ARHR), and hypophosphataemic rickets with hyperparathyroidism. Second- those with normal or low FGF23, which are caused by gene mutations in renal tubular phosphate transporters and include hereditary hypophosphataemic rickets with hypercalciuria (HHRH) and X-linked recessive hypophosphataemic rickets. The radiographical changes and clinical features of rickets in various types of HR are similar but not identical. Short stature, bone deformities mainly in the lower limbs, and dental problems are typical characteristics of HR. Although the initial diagnosis of HR is usually based on physical, radiological, and biochemical features, molecular genetic analysis is important to confirm the diagnosis and differentiate the type of HR. In this review, we describe clinical and biochemical features as well as genetic causes of different types of HR. The clinical and biochemical characteristics presented in this review can help in the diagnosis of different types of HR and, therefore, direct genetic analysis to look for the specific gene mutation.

Hypophosphatemic rickets (HR) is a genetic disease of phosphate wasting that is characterized by defective bone mineralization. The most common cause of the disease is mutations in the phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX) gene. The aims of this study were to identify the gene variants responsible for HR in three cases of Malaysian origin from three independent families and to describe their clinical, biochemical, and radiological features. Whole exome sequencing (WES) was performed on all patients and their parents, followed by Sanger sequencing validation. Bioinformatics tools were used to provide supporting evidence for pathogenicity of variants. To confirm that a mutation is de novo, paternity test was carried out. High resolution melting curve analysis was performed to assess the allele frequency in normal controls for mutations that were found in the patients. The patients showed typical characteristics of HR including lower limb deformity, hypophosphatemia, and elevated alkaline phosphatase. WES revealed two variants in the PHEX gene and one variant in the dentin matrix protein 1 (DMP1) gene. Two of the three variants were novel, including c.1946_1954del (p.Gly649_Arg651del) in PHEX and c.54 + 1G > A in DMP1. Our data suggests that the novel p.Gly649_Arg651del variant is likely pathogenic for HR disease. This study extends the variant spectrum of the PHEX and DMP1 genes. Our findings indicate that WES is an advantageous approach for diagnosis of genetic diseases which are heterogeneous.

Objectives PAX4 (Paired box 4), a transcription factor crucial in pancreatic beta cell development and function, is a rare cause of maturity-onset diabetes of the young (MODY). What is new? A novel PAX4 variant is verified by family segregation study to be likely pathogenic. A child below 10 years of age diagnosed to have PAX4-MODY, differing from previously reported paediatric cases diagnosed in adolescence. Case presentation A child with diabetes diagnosed at age 8 years, harbored a PAX4 variant, c.890G>A (p.Gly297Asp), initially classified as variant of uncertain significance. Eleven family members (7 adults and 4 children) with and without diabetes across 3 generations were genotyped. The variant co-segregated with diabetes or prediabetes across 3 generations of the family. The variant is reclassified as likely pathogenic according to standard guidelines. Conclusion Genetic testing is essential to confirm PAX4-MODY as the presentation is variable even within the same family. PAX4 mutation needs to be considered in MODY genetic testing in Asian patients.

IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband's genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband's brother had intellectual disability while the proband had normal development. This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment.