OBJECTIVES: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. METHODS: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. RESULTS: The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (r_s=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (r_s=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). CONCLUSIONS Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.
Child ; Humans ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors ; Familial Hypophosphatemic Rickets/diagnosis* ; Rickets, Hypophosphatemic/diagnosis*

Chronic hypophosphatemia caused by decreased intestinal absorption or increased renal clearance, may lead to rickets or osteomalacia independently of other predisposing abnormalities. The conditions commonly associated with increased renal clearance of phosphate are X-linked hypophosphatemic rickets, tumor associated rickets/osteomalacia, RTA and Fanconi syndrome. Recently we experienced 3 men with adult-onset, histologically proven osteomalacia associated with increased renal clearance of phosphate. None of them had a family history of bone disease, tumors or other tubular defects. All of these had remarkable biochemical and clinical improvement with medical treatment such as 1, 25-dihydroxyvitamin D and phosphate supplementation. Although we did not find tumors yet, we could not rule out the possibility of tumor-associated osteomalcia since it often takes several years to make a diagnosis because of small size, benign nature and unusual location of tumors. Thus, careful long-term follow up for tumor occurrence will be maintained in these patients with sporadic nonfamilial hypophosphatemic osteomalacia.
Bone Diseases ; Diagnosis ; Familial Hypophosphatemic Rickets ; Fanconi Syndrome ; Follow-Up Studies ; Humans ; Hypophosphatemia ; Intestinal Absorption ; Male ; Osteomalacia ; Rickets

OBJECTIVE: To detect pathological variant in a Chinese pedigree affected with X-linked hypophosphatemia (XLH). METHODS: Whole-exome sequencing was carried out to screen genetic variants in the proband and her parents. Candidate variant of the phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX) was verified by Sanger sequencing of all members of the pedigree and the 100 healthy controls. Prenatal diagnosis was carried out on chorionic villi sample derived from the fetus of the proband. RESULTS: A c.1256G>A (p. Gly419Glu) variant was identified in the PHEX gene of the proband and all other patients from this pedigree. The same variant was not found among healthy members from this pedigree and the 100 healthy controls. Prenatal diagnosis suggested that the fetus also carried the c.1256G>A (p. Gly419Glu) variant. CONCLUSION The c.1256G>A (p. Gly419Glu) variant of the PHEX gene probably underlay the pathogenesis of XLH in this family. Discovery of the novel variant has enriched the mutational spectrum of the PHEX gene.
China ; Familial Hypophosphatemic Rickets ; Female ; Humans ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase/genetics* ; Pedigree ; Pregnancy ; Prenatal Diagnosis

PURPOSE: Hypophosphatemic rickets is a hereditary disease, characterized by hypophosphatemia due to renal phosphate wasting, impaired renal production of 1,25-dihydroxyvitamin D3, rachitic bone deformities and impaired growth. The purpose of this study is to provide clinical profiles of patients with hypophosphatemic rickets in our hospital. METHODS: Between July 1983 and February 2004, 56 patients were diagnosed as having hypophosphatemic rickets. The medical records of these patients were reviewed retrospectively. Clinical manifestations, family histories, laboratory data, treatment outcomes were described. RESULTS: Fifty six patients were enrolled in this study. The average age at symptom onset and diagnosis were 20 months and 5 years respectively. Fourteen patients had family histories. The main clinical manifestations were bow legs and short stature. There was a significant negative correlation between the ages and the height z-scores at the time of diagnosis(r=-0.47, P=0.005). Initial laboratory data showed normocalcemia, hypophosphatemia, elevated serum alkaline phosphatase, decreased tubular reabsorption of phosphate and a normal range of 1,25-dihydroxyvitamin D3. Radiographic examinations of bone revealed fraying, widening and cupping of the metaphyseal ends. Treatment consisted of Joulie solution and vitamin D metabolites, and resulted in improved biochemical and radiographic findings. However, height z-scores remained essentially unchanged(P=0.224). Complications of treatment were frequently observed, including hyperparathyroidism, nephrocalcinosis, and hypercalciuria. Sixteen patients had corrective osteotomy and 4 of them underwent leg lengthening together. CONCLUSION: There was a gap of several years between the onset of symptoms and the diagnosis. Early treatment seems to be essential to growth. For the earlier treatment, the offsprings of affected parents should be followed up closely.
Alkaline Phosphatase ; Calcitriol ; Congenital Abnormalities ; Diagnosis ; Familial Hypophosphatemic Rickets ; Genetic Diseases, Inborn ; Genu Varum ; Humans ; Hypercalciuria ; Hyperparathyroidism ; Hypophosphatemia ; Hypophosphatemia, Familial ; Leg ; Medical Records ; Nephrocalcinosis ; Osteotomy ; Parents ; Reference Values ; Retrospective Studies ; Rickets, Hypophosphatemic* ; Vitamin D

OBJECTIVETo explore the clinical characteristics and genetic mutation in a family affected with hypophosphatemic rickets.

METHODSWhole exome sequencing (WES) was used to screen potential mutations in genomic DNA extracted from peripheral venous blood sample from the proband. Suspected mutation was confirmed with Sanger sequencing. Amniotic fluid was sampled from the proband for prenatal diagnosis. Potential maternal contamination was excluded by analysis of short tandem repeat (STR) markers.

RESULTSWES has identified a heterozygous c.2058_2059insAGTT (p.L686fs) mutation of the PHEX gene in the proband, which was confirmed by Sanger sequencing in other affected individuals from the family. The mutation was detected in the amniotic fluid sample from the fetus but not among healthy members from the family.

CONCLUSIONIdentification of the PHEX mutation by WES has facilitated genetic counseling and prenatal diagnosis for the family affected with hypophosphatemic rickets.

Adult ; DNA Mutational Analysis ; Exome ; Familial Hypophosphatemic Rickets ; diagnosis ; genetics ; Female ; Humans ; Microsatellite Repeats ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase ; genetics ; Pregnancy ; Prenatal Diagnosis ; Whole Genome Sequencing

We present the cytologic features of small cell neuroendocrine carcinoma of the liver metastasized from the uterine cervix. Cytologically, tumor cells were arranged in a pat- tern of solid sheet in necrotic background. The tumor cells were characterized by uniform, small cells, round hyperchromatic nuclei, and high nuclear cytoplasmic ratio. The smears showed frequent mitotic figures and rosette formation, These findings were identified with the previous histologic sections of uterine cervix. To make a diagnosis of metastatic small cell neuroendocrine carcinoma on the Papanicolaou smear, a high index of suspicion and careful review of clinical history are needed
Animals ; Carcinoma, Neuroendocrine ; Cervix Uteri ; Charadriiformes ; Cytoplasm ; Diagnosis ; Familial Hypophosphatemic Rickets* ; Female ; Fibrous Dysplasia, Polyostotic* ; Liver ; Papanicolaou Test ; Rosette Formation ; Vitamin D* ; Vitamins*

X-linked hypophosphatemia (XLH) is a hereditary metabolic disease caused by the loss of phosphate through the renal tubules into the urine, and an associated decrease in serum calcium and potassium phosphate. Its dental features include spontaneous dental abscesses that occur in the absence of trauma or dental caries. The aim of this case report was to describe the dental problems of XLH patients and to evaluate limitations in their treatment. A 14 year old male and a 38 year old female with XLH were referred to the Department of Conservative Dentistry for endodontic treatment. The dental findings were periapical abscesses without obvious trauma or caries. Conservative endodontic treatment was performed in teeth with pulp necrosis and abscess. In case 1, the treated teeth showed improvements in bone healing, without clinical symptoms. However, in case 2, the implants and the treated tooth showed hypermobility, and the final restoration was therefore postponed. Early diagnosis, periodic examinations, and communication with the patient's pediatrician are important in the dental management of patients with XLH.
Abscess ; Calcium ; Dental Caries ; Dental Pulp Necrosis ; Dentistry ; Early Diagnosis ; Familial Hypophosphatemic Rickets* ; Female ; Humans ; Hypophosphatemia ; Male ; Metabolic Diseases ; Periapical Abscess ; Potassium ; Tooth

There are currently no published cases that report concomitant Turner syndrome (TS), 2q37 deletion syndrome and X-linked hypophosphatemic rickets (XLH). Interestingly, since the clinical phenotypes of TS and 2q37 deletion syndrome overlap, the correct diagnosis may be missed without a standardized approach to genetic testing consisting of both karyotype and microarray. Both chromosome anomalies have been associated with short stature and a variety of skeletal abnormalities however to date no reports have associated these syndromes in association with a phosphate regulating endopeptidase homolog, X-linked (PHEX) gene deletion resulting in XLH. We report a 3-year-old female with 3 concurrent genetic disorders including a 9.98 Mb terminal deletion of chromosome 2: del(2)(q37.1;q37.3), XLH secondary to a small microdeletion of part of the PHEX gene, and mosaic TS (mos 45,X[32]/46,X[18]). This is the first case report of a patient with 2q37 deletion syndrome and mosaic TS (mos 45,X[32]/46,X[18]) found to have XLH secondary to an interstitial constitutional PHEX gene deletion. Her severe phenotype and multiple genotypic findings reinforce the importance of thorough genetic testing in the setting of complicated phenotypic presentations.
Bone Diseases ; Child, Preschool* ; Chromosomes, Human, Pair 2 ; Diagnosis ; Familial Hypophosphatemic Rickets* ; Female* ; Gene Deletion ; Genetic Testing ; Humans ; Karyotype ; Microarray Analysis ; Phenotype ; PHEX Phosphate Regulating Neutral Endopeptidase ; Turner Syndrome*

Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments.
Absorption ; Alkaline Phosphatase ; Calcium ; Chondrocytes ; Collagen ; Diagnosis ; Durapatite ; Enzyme Replacement Therapy ; Extracellular Matrix ; Extracellular Vesicles ; Familial Hypophosphatemic Rickets ; Fibroblast Growth Factors ; Gene Expression ; Humans ; Hypophosphatasia ; Hypophosphatemia ; Metabolism ; Miners ; Osteoblasts ; Osteocytes ; Prognosis ; Quality of Life ; Receptors, Fibroblast Growth Factor ; Rickets ; Signal Transduction ; Vitamin D ; Vitamin D Deficiency