A 53-year woman and her 18-year daughter presenting with bone pain, bone fractures, bone deformities and short stature were admitted to Gansu Provincial People′s Hospital in March 2021. Laboratory tests showed low blood phosphorus, low renal phosphorus threshold, normal or low blood calcium, and normal or increased PTH. The high-throughput sequencing indicated heterozygous mutations of the PHEX gene (Phosphate-regulating gene with Homology to Endopeptidases on the X chromosome) in two patients, which was not detected in other family members; finally the diagnosis of X-linked dominant hypophosphatemic rickets/osteomalacia(XLH)was confirmed for these two patients. Treated with neutral phosphorus solution and Rocaltrol, bone pain was relieved completely in the younger patient, but not for her mother due to long disease course and severe complications. Because of the large heterogeneity of the disease there are high missed diagnosis and misdiagnosis rates for XLH. In this paper a pedigree of XLH is reported with literature review.

Objective The aims of the study were to investigate the effects of human islet amyloid polypeptide (hIAPP) on autophagy in INS-1 cells and its underlying mechanism,and to explore the role of autophagy in hIAPP-induced cytotoxicity and oxidative stress.Methods INS-1 cells were treated with hIAPP (10 μmol/L) for 24 h in the presence or absence of N-acetyl-L-cysteine (NAC),compound C,5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and 3-methyladenine (3-MA),respectively.Transmission electron microscopy was used to observe the number of autophagosome in cells.Cell viability was determined by methyl thiazolyl tetrazolium (MTT) test.2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to measure the relative levels of reactive oxygen species (ROS).Western blot was used to detect expression of adenosine monophosphate-activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain3 (LC3).Results Treatment of INS-1 cells with hIAPP resulted in a significant increase in the number of autophagosomes and the expression of LC3-Ⅱ/LC3-Ⅰ (both P＜0.05).Meanwhile,treatment of INS-1 cells with hIAPP enhanced the level of ROS to 1.76 times of control cells (P＜0.01).Co-treatment with NAC,an antioxidant,inhibited hIAPP-induced ROS generation,and the expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK in the INS-1 cells (all P＜0.05).Pretreatment of INS-1 cells with AMPK inhibitor compound C suppressed hIAPP and AICAR,an activator of AMPK,induced expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK (all P＜0.05).Autophagic inhibitor 3-MA and compound C aggravated the hIAPP-induced cell death and ROS generation in INS-1 cells (All P＜0.05).The cytotoxic effects of hIAPP were significantly attenuated by co-treatment with AICAR (P＜0.05).Conclusion Autophagy may act as an adaptive mechanism to alleviate hIAPP-induced oxidative damage and toxicity in INS-1 cells.