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Purpose: Lipocalin 2 (LCN2) is a newly recognized bone-derived factor that is important in regulation of energy metabolism. We investigated the correlation of serum LCN2 levels and glycolipid metabolism, and body composition in a large cohort of patients with osteogenesis imperfecta (OI). Methods: A total of 204 children with OI and 66 age- and gender-matched healthy children were included. Circulating levels of LCN2 and osteocalcin were measured by enzyme-linked immunosorbent assay. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated chemical analyzers. The body composition was measured by dual-energy X-ray absorptiometry. Grip strength and timed-up-and-go (TUG) were tested to evaluate the muscle function. Results: Serum LCN2 levels were 37.65 ± 23.48 ng/ml in OI children, which was significantly lower than those in healthy control (69.18 ± 35.43 ng/ml, P< 0.001). Body mass index (BMI) and serum FBG level were significantly higher and HDL-C levels were lower in OI children than healthy control (all P< 0.01). Grip strength was significantly lower (P< 0.05), and the TUG was significantly longer in OI patients than healthy control (P< 0.05). Serum LCN2 level was negatively correlated to BMI, FBG, HOMA-IR, HOMA-β, total body, and trunk fat mass percentage, and positively correlated to total body and appendicular lean mass percentage (all P< 0.05). Conclusions: Insulin resistance, hyperglycemia, obesity, and muscle dysfunction are common in OI patients. As a novel osteogenic cytokine, LCN2 deficiency may be relevant to disorders of glucose and lipid metabolism, and dysfunction of muscle in OI patients.

Aims: To investigate genotype and phenotype of congenital nephrogenic diabetes insipidus caused by AVPR2mutations, which is rare and limitedly studied in Chinese population. Methods: 88 subjects from 28 families with NDI in a department (Beijing, PUMCH) were screened for AVPR2mutations. Medical records were retrospectively reviewed and characterized. Genotype and phenotype analysis was performed. Results: 23 AVPR2mutations were identified, including six novel mutations (p.Y117D, p.W208R, p.L313R, p.S127del, p.V162Sfs*30 and p.G251Pfs*96). The onset-age ranged from 1 week to 3 years. Common presentations were polydipsia and polyuria (100%) and intermittent fever (57%). 21% and 14% of patients had short stature and mental impairment. Urine SG and osmolality were decreased, while serum osmolality and sodium were high. Urological ultrasonography results showed hydronephrosis of the kidney (52%), dilation of the ureter (48%), and thickened bladder wall or increased residual urine (32%), led to intermittent urethral catheterization (7%), cystostomy (11%) and binary nephrostomy (4%). Urological defects were developed in older patients. Genotype and phenotype analysis revealed patients with non-missense mutations had higher levels of serum sodium than missense mutations. Conclusion: In the first and largest case series of NDI caused by AVPR2mutations in Chinese population, we established genetic profile and characterized clinical data, reporting six novel mutations. Further, we found genotype was associated with phenotype. This knowledge broadens genotype and phenotype spectrum of rare congenital NDI caused by AVPR2mutations, and provides basis for studying molecular biology of AVPR2.