Introduction 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. It also leads to low serum 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. XLH in children and adolescents also causes impaired growth, myopathy, bone pain, and dental abscesses. XLH is the most frequent inherited cause of phosphopenic rickets/osteomalacia. Hypophosphatemia is also found in calcipenic rickets/osteomalacia as a result of secondary hyperparathyroidism. Thus, chronic hypophosphatemia is a common etiologic factor in all types of rickets. Results There is considerable overlap between symptoms and signs of phosphopenic and calcipenic rickets/osteomalacia. Wrong diagnosis leads to inappropriate treatment of rickets/osteomalacia. Nutritional rickets and osteomalacia are common in the Gulf Cooperation Council countries which include Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Due to high levels of consanguinity in the region, genetic causes of phosphopenic and calcipenic rickets/osteomalacia are also common. Conclusion This guideline was developed to provide an approach to the diagnosis of XLH, especially where there is no family history of the disease, and that other related conditions are not mistaken for XLH. We also guide the medical management of XLH with conventional treatment and with burosumab, a recombinant human IgG1 monoclonal antibody to FGF23.

Obesity is associated with an increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) which is a multi-factorial disease associated with a dysregulated metabolism and can be prevented in pre-diabetic individuals with impaired glucose tolerance. A metabolomic approach emphasizing metabolic pathways is critical to our understanding of this heterogeneous disease. This study aimed to characterize the serum metabolomic fingerprint and multi-metabolite signatures associated with IR and T2DM. Here, we have used untargeted high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) to identify candidate biomarkers of IR and T2DM in sera from 30 adults of normal weight, 26 obese adults, and 16 adults newly diagnosed with T2DM. Among the 3633 peak pairs detected, 62% were either identified or matched. A group of 78 metabolites were up-regulated and 111 metabolites were down-regulated comparing obese to lean group while 459 metabolites were up-regulated and 166 metabolites were down-regulated comparing T2DM to obese groups. Several metabolites were identified as IR potential biomarkers, including amino acids (Asn, Gln, and His), methionine (Met) sulfoxide, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, serotonin, L-2-amino-3-oxobutanoic acid, and 4,6-dihydroxyquinoline. T2DM was associated with dysregulation of 42 metabolites, including amino acids, amino acids metabolites, and dipeptides. In conclusion, these pilot data have identified IR and T2DM metabolomics panels as potential novel biomarkers of IR and identified metabolites associated with T2DM, with possible diagnostic and therapeutic applications. Further studies to confirm these associations in prospective cohorts are warranted.