GATM-related Fanconi renotubular syndrome 1 (FRTS1) is a form of renal Fanconi syndrome (RFS), which is a disorder of solute and water reabsorption caused by defects in the function of the entire proximal tubule. Recent findings reveal the molecular basis of FRTS1: Intramitochondrial fiber aggregation triggered by mutant GATM provides a starting point for proximal tubule damage and drives disease progression. As a rare and newly recognized inherited kidney disease, the complex manifestations of FRTS1 are easily underdiagnosed or misdiagnosed. We discuss the complex phenotype of a 26-year-old woman with onset in infancy and a long history of hypophosphatemic rickets. We also identified a novel heterozygous missense variant in the GATM gene in this patient. The novel variant and phenotype we report expand the disease spectrum of FRTS1. We recommend screening for GATM in children with RFS, especially in patients with resistant rickets who have previously had negative genetic testing. In addition, we found pathological deposition of mutant GATM proteins within mitochondria in the patient\'s urinary sediment cells by a combination of electron microscopy and immunofluorescence. This unique urine cytology experiment has the potential to be a valuable tool for identifying patients with RRTS1.

We aimed to determine the onset time of hypophosphatemic rickets and investigate the mechanism of motility impairment through adenosine triphosphate (ATP) production in goslings. Two hundred and sixteen 1-day-old male Jiangnan white geese were randomly divided into 3 groups, with 6 replicates and 12 geese per replicate. Birds were fed on 3 diets: a control diet (nonphytic phosphorus, NPP, 0.38%), a P-deficient diet (PD; NPP, 0.08%), and a high P diet (HP; NPP, 0.80%) for 14 d. Subsequently, all birds were shifted to the control diet for an additional 14 d. The cumulative incidence of lameness increased significantly (P < 0.01) starting on d 4, reaching over 80% on d 7 and 100% on d 12 in the PD group. Drinking and eating frequency decreased from d 4 and d 5, respectively, in the PD group compared to the other groups (most P < 0.01). The PD group exhibited shorter and narrower beaks, higher (worse) curvature scores of the beak and costochondral junctions, swelling caput costae, and dirtier feathers since d 4, in contrast to the control and HP groups (most P < 0.01). The HP had bigger (P < 0.05) beak and sternum sizes than the control groups on d 4 to 11. Leg muscle ATP levels were lower (P < 0.01 or 0.05) on d 4 to 11; in contrast, adenosine diphosphate (d 7-11) was higher in PD compared to the control (P < 0.05). Leg muscle ATP level had positive linear (R2 > 0.40) correlations (r > 0.60) with eating and drinking frequencies on d 7 and 11 (P < 0.01). Bone stiffness, feather cleanliness, and ATP levels recovered (P > 0.05) to the control level, whereas bone size did not recover (P < 0.05) in PD and HP after eating the control diet for 2 wk. The onset time of hypophosphatemic rickets was around 4 d in goslings, and insufficient leg muscle ATP was related to the impaired motility observed in early P-deficient geese.

BACKGROUND: Rickets occurs in infants and children (aged 2 months to 3 years), compromising their skeletal development and damaging nervous, hematopoietic, immune, and other system functions. This study aimed to explore the significance of CD38 in rickets.
METHODS: The microarray dataset GSE22523 was analyzed to obtain differentially expressed genes in rickets patients. A total of 36 rickets patients and healthy controls were recruited for the study, and their blood samples were collected, followed by detecting mRNA levels of CD38 using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the significance of CD38 in rickets patients was analyzed by receiver operating characteristic (ROC) analysis, while the correlation between CD38 and 25-hydroxy-vitamin D (25OHD)/parathyroid hormone (PTH) was analyzed with Pearson\'s correlation.
RESULTS: Results showed that CD38 mRNA levels and PTH contents were significantly increased in the rickets patients while 25OHD contents were decreased. Correlation analysis indicated that CD38 was positively correlated with PTH and negatively correlated with 25OHD in both serum and plasma samples of rickets patients. Moreover, ROC analysis showed that serum CD38 was 0.9005 (95 % CI: 0.8313-0.9696), and the AUCs of plasma CD38 was 0.7215 (95 % CI: 0.6031-0.8398) in differentiating rickets patients from healthy persons, advocating serum CD38 had better diagnostic value.
CONCLUSIONS: CD38 mRNA levels were upregulated in rickets patients and closely correlated with PTH and 25OHD contents, indicating CD38 might be a diagnostic marker of rickets patients. Further research on the diagnostic utility of CD38 is necessary for the diagnosis and treatment of ricketsin rickets in the future.

Hypovitaminosis D during infancy is associated with the development of chronic diseases and poor health later in life. While the effect of environmental factors on vitamin D concentration has been extensively explored, this study aimed to explore the effect of genetic factors on vitamin D concentration among Chinese infants. We conducted a multi-centre cross-sectional study in Hong Kong from July 2019 to May 2021. A candidate genetic approach was adopted to study four selected genetic variants of the vitamin D-binding protein (DBP) and vitamin D receptor (VDR) (rs4588, rs7041, rs2282679 and rs2228570) to examine their associations with measured serum 25(OH)D concentration. A total of 378 Chinese infants aged 2-12 months were recruited in this study. Peripheral blood samples were collected from the infants to measure serum 25(OH)D concentration and extract DNA. Results showed that rs7041T and rs2282679C were significantly associated with lower serum 25(OH)D concentration. Further analysis of the DBP variants revealed that the GC1F allele was significantly associated with lower 25(OH)D concentration and identified as the risk DBP isoform in infants. While our results revealed that there is no direct association between VDR-FokI genotype and serum 25(OH)D concentration, a VDR-FokI genotype-specific pattern was observed in the association between DBP isoforms and serum 25(OH)D concentration. Specifically, significant associations were observed in the DBP genotypes GC1F/F, GC1F/2 and GC1S/2 among VDR-FokI TT/TC carriers, but not in VDR-FokI CC carriers. Our findings lay down the basis for the potential of genetic screening to identify high risk of hypovitaminosis D in Chinese infants.

OBJECTIVE: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD.
METHODS: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected.
RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L).
CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Bursicon, a neuropeptide hormone comprising two subunits-bursicon (burs) and partner of burs (pburs), belongs to the cystine-knot protein family. Bursicon heterodimers and homodimers bind to the lucine-rich G-protein coupled receptor (LGR) encoded by rickets to regulate multiple physiological processes in arthropods. Notably, these processes encompass the regulation of female reproduction, a recent revelation in Tribolium castaneum. In this study we investigated the role of burs/pburs/rickets in mediating female vitellogenesis and reproduction in a hemipteran insect, the whitefly, Bemisia tabaci. Our investigation unveiled a synchronized expression of burs, pburs and rickets, with their transcripts persisting detectable in the days following eclosion. RNAi-mediated knockdown of burs, pburs or rickets significantly suppressed the transcript levels of vitellogenin (Vg) and Vg receptor in the female whiteflies. These effects also impaired ovarian maturation and female fecundity, as evidenced by a reduction in the number of eggs laid per female, a decrease in egg size and a decline in egg hatching rate. Furthermore, knockdown of burs, pburs or rickets led to diminished juvenile hormone (JH) titers and reduced transcript level of Kruppel homolog-1. However, this impact did not extend to genes in the insulin pathway or target of rapamycin pathway, deviating from the results observed in T. castaneum. Taken together, we conclude that burs/pburs/rickets regulates the vitellogenesis and reproduction in the whiteflies by coordinating with the JH signaling pathway.

Family with sequence similarity 20-member C (FAM20C) is a kinase specific to most of the secreted phosphoproteome. FAM20C has been identified as the causative gene of Raine syndrome, initially characterized by lethal osteosclerosis bone dysplasia. However, since the identification of the cases of nonlethal Raine syndrome characterized by hypophosphatemia rickets, the previous definition of Raine syndrome has become debatable and raised a question about the role of mutations of FAM20C in controversial skeletal manifestation in the two forms of the disease. In this study, we aimed to investigate the influence of FAM20C mutations on skeletogenesis. We developed transgenic mice expressing Fam20c mutations mimicking those associated with human lethal and nonlethal Raine syndrome. The results revealed that transgenic mice expressing the mutant Fam20c found in the lethal (KO;G374R) and nonlethal (KO;D446N) Raine syndrome exhibited osteomalacia without osteosclerotic features. Additionally, both mutants significantly increased the expression of the Fgf23, indicating that Fam20c deficiency in skeletal compartments causes hypophosphatemia rickets. Furthermore, as FAM20C kinase activity catalyzes the phosphorylation of secreted proteomes other than those in the skeletal system, global FAM20C deficiency may trigger alterations in other systems resulting in osteosclerosis secondary to hypophosphatemia rickets. Together, the findings of this study suggest that FAM20C deficiency primarily causes hypophosphatemia rickets or osteomalacia; however, the heterogeneous skeletal manifestation in Raine syndrome was not determined solely by specific mutations of FAM20C. The findings also implicated that rickets or osteomalacia caused by FAM20C deficiency would deteriorate into osteosclerosis by the defects from other systems or environmental impacts.

UNASSIGNED: To investigate the effectiveness of single Taylor external fixator combined with biplanar osteotomy on correction of tibial multiplanar deformities.
UNASSIGNED: Between October 2016 and December 2021, 11 patients with tibial multiplanar deformities (20 sides) were treated with single Taylor external fixator and biplanar osteotomy. Of them, 4 were male and 7 were female; the average age ranged from 13 to 33 years (mean, 21.9 years). Diagnosis included rickets severe genu varum deformity (7 cases, 14 sides), rickets severe genu valgum deformity (2 cases, 4 sides), multiple osteochondromatosis calf deformity (1 case, 1 side), neurofibromatosis medial lower leg anterior arch deformity with short of leg (1 case, 1 side). After fibular osteotomy and tibial multiplanar osteotomy, a Taylor external fixator was installed. After operation, the deformities were corrected successively and fixed completely. The osteotomy healed, then the external fixator was removed. Before operation and at 12 months after operation, the full-length X-ray films were taken. The leg-length discrepancy, medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), and tibial rotation angle were measured. The degree of lower limb deformity was scored with reference to a customized tibial mechanical axis scoring table.
UNASSIGNED: Osteotomy was successfully completed without neurovascular injury and other complications. The external fixator was adjusted for 28-46 days, with an average of 37 days, and the external fixator was worn for 136-292 days, with an average of 169 days. Mild needle infection during the fixation period occurred in 3 sides, refracture at the distal tibial osteotomy in 1 side after removing the external fixator, and nonunion of the distal fibular osteotomy in 1 side. All patients were followed up 369-397 days (mean, 375 days). At 12 months after operation, the lower limb discrepancy decreased, but there was no significant difference ( P>0.05). MPTA, LDTA, PPTA, ADTA, and tibial rotation angle improved, and the differences in LDTA, ADTA, and tibial rotation angle were significant ( P<0.05). The score of lower limb deformity was significantly higher than that before operation ( P<0.05), and the results were excellent in 9 sides, good in 8 sides, fair in 3 sides, with the excellent and good rate of 85%.
UNASSIGNED: Single Taylor external fixator combined with biplanar osteotomy is effective in the correction of tibial multiplanar deformities.
UNASSIGNED: 探讨应用单套Taylor外固定架联合双平面截骨矫正胫骨多平面畸形的疗效。.
UNASSIGNED: 2016年10月—2021年12月，采用单套Taylor外固定架联合双平面截骨治疗11例（20侧）胫骨复杂多平面畸形患者。其中男4例，女7例；年龄13～33岁，平均21.9岁。佝偻病重度O型腿畸形7例（14侧）、佝偻病重度X型腿畸形2例（4侧），多发性骨软骨瘤病小腿畸形1例（1侧），神经纤维瘤病小腿中下段前弓畸形合并短缩1例（1侧）。术中行腓骨截骨以及胫骨两个畸形平面截骨后，安装Taylor外固定架；术后双平面畸形依次矫正后再整体固定，待截骨愈合后拆除外固定架。术前及术后12个月摄双下肢全长X线片，测算双下肢长度差值以及与胫骨机械轴评价相关的指标，包括胫骨近端内侧角（medial proximal tibial angle，MPTA）、胫骨远端外侧角（lateral distal tibial angle，LDTA）、胫骨近端后倾角（posterior proximal tibial angle，PPTA）、胫骨远端前倾角（anterior distal tibial angle，ADTA）以及胫骨旋转角度；参照自定胫骨机械轴评分表评价小腿畸形程度。.
UNASSIGNED: 截骨手术均顺利完成，未出现神经、血管损伤等并发症。术后矫形顺利，外固定架调整矫形时间28～46 d，平均37 d；外固定架佩戴时间136～292 d，平均169 d。3侧带架期间轻度针道感染，1侧拆除外固定架后出现胫骨远端截骨处再骨折，1侧腓骨远端截骨不愈合。患者均获随访，随访时间369～397 d，平均375 d。术后12个月，双下肢长度差值较术前减小，但差异无统计学意义（ P>0.05）；MPTA、LDTA、PPTA、ADTA、胫骨旋转角度均较术前改善，其中LDTA、ADTA、胫骨旋转角度手术前后差异有统计学意义（ P<0.05）。根据自定胫骨机械轴评分表，下肢畸形评分较术前提高（ P<0.05）；其中获优9侧，良8侧，中3侧，优良率达85%。.
UNASSIGNED: 应用单套Taylor外固定架联合双平面截骨可有效矫正胫骨多平面畸形。.

Vitamin D-dependent rickets (VDDR) type 1A is a rare autosomal recessive disorder caused by cytochrome P450 family 27 subfamily B member 1 (CYP27B1) mutations and can lead to deficiencies in 1α-hydroxylase activity. The present study describes the case of a 39-year-old male patient who presented with rickets and deformities of limbs. Blood biochemical analysis revealed hypocalcemia and high serum parathyroid hormone (PTH) levels. Whole-exome Sanger sequencing using peripheral venous blood of this patient and his parents revealed exon1 c.182T>C, a novel mutation. Through physical examination, laboratory tests, imaging including lower limbs and lumbar spine X-ray and pelvis CT scan, and genetic testing, the patient was diagnosed with VDDR-1A. Following 1 month of treatment with 0.5 µg 1,25-dihydroxy-vitamin D3 twice daily and 0.6 g calcium carbonate once daily, follow-up examinations revealed that the patient\'s PTH and serum calcium levels had returned to normal. As the patient was diagnosed in his adulthood and missed the optimal treatment period, he developed irreversible deformities. If VDDR-1A can be diagnosed during infancy and childhood, skeletal deformities may be prevented. Therefore, the present report supports the proposal of early genetic sequencing in children with calcium deficiencies for the early diagnosis of rare diseases such as VDDR-1A, -1B and -2A and hereditary hypophosphatemic rickets. Since VDDR-1A diagnosed in adults is rare, the present case may provide clinicians with further insights into the characteristics of this rare disease.

This study aimed to explore the vitamin D status of children in northern China and the association between vitamin D and glucose metabolism.
Cross-sectional study was conducted among child participants and retrospective study designs were conducted among adult participants.
Both studies were recruited from Harbin, 326 children were included in children\'s study, 8469 adults were included in adult study.
Physical examination, lifestyle and dietary habit data were recorded in all the participants. Serum insulin, glucose, 25(OH)D3 concentrations in children and serum glucose and lipids levels in adults were measured. Rickets history was also investigated in adults, which was used to define vitamin D deficiency in childhood. The associations were tested by linear regression and binary logistic regression.
In the children\'s study, only 10.7% of participants were vitamin D sufficient (≥30 ng/mL). Inverse correlations between serum 25(OH)D3 concentration and fasting insulin and homeostasis model assessment - insulin resistance (HOMA-IR) were found, and children with lower serum 25(OH)D3 concentrations were likely to have insulin resistance (IR) (OR: 0.955, 95% CI: 0.917 to 0.995, p value: 0.027). In an adult study, rickets in childhood increased the risk of type 2 diabetes in male participants (OR=1.414, 95% CI=1.013 to 1.972; p value=0.042), but this result was not observed in female participants.
Our findings suggest that vitamin D deficiency is widespread in northern China. Vitamin D deficiency in childhood was associated with IR and increased the risk of type 2 diabetes in male adults.