Faculty

Muhammad Yazid Jalaludin

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Approach to the diagnosis of Hypophosphatemic rickets

X-linked hypophosphatemia (XLH) is a rare inherited cause of hypophosphatemic rickets and
osteomalacia. It is caused by mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX). This results in increased plasma fibroblast growth factor-23 (FGF23), which leads to loss of renal sodium-phosphate co-transporter expression leading to chronic renal phosphate excretion. Raised plasma FGF23 also suppresses the production of 1,25 dihydroxyvitamin D (1,25(OH)2D), resulting in impaired intestinal phosphate absorption.

Chronic hypophosphatemia in XLH leads to impaired endochondral mineralization of the growth plates of long bones with bony deformities. Children with XLH develop genu varum or valgum upon weightbearing, widening of ends of long bones, abnormal head shape due to craniosynostosis, progressive and disproportionate decline in linear growth, muscle weakness, bone pain, and dental abscesses due to impaired mineralization of enamel and dentine.

XLH is the most frequent inherited cause of phosphopenic rickets/osteomalacia. As hypophosphatemia is also found in calcipenic rickets/osteomalacia as a result of secondary hyperparathyroidism, it is very important to get a detailed medical, including the family history, auxology, and musculoskeletal examination, and appropriate investigation (radiology, biochemistry, and genetic studies) in the course of establishing the XLH diagnosis. This approach can help to exclude other causes of phosphopenic and calcipenic rickets/osteomalacia.

Emerging therapies for obesity and Type 2 DM

Type 2 diabetes mellitus (T2DM), once considered an illness of older adults is increasingly affecting more children. Sedentary lifestyles, unhealthy eating, obesity and insulin resistance contribute to an explosive increase in the incidence. Children with T2DM have the risk of developing complications in early adulthood, which would place a significant burden on the family and society.

Type 2 DM in children most often occurs during the second decade of life, with a mean age of diagnosis of ∼13.5 years which coincides with the peak physiologic pubertal insulin resistance. It affects mainly obese children of all races but at a much greater prevalence in those of non-white European descent such as African, native North American, Hispanic, Asian, South Asian (Indian Peninsula) and Native Pacific Islanders.

Treatment options in paediatric obesity and T2DM is limited, with lifestyle and behavior modifications as the mainstay of management. For decades, the only FDA approved drugs for T2DM are metformin and insulin. Recently, FDA has approved the use of liraglutide for T2DM children aged 10-17 years (July 2019) and obese adolescents aged 12-17 years (December 2020). Few other drugs for use in paediatric T2DM population are currently under research, although these drugs have been proven to be effective and safe in adults.

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