Did you mean: hypophosphatemic rickets
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Bone Reports Jun 2024Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast... (Review)
Review
INTRODUCTION
Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor.
MATERIAL AND METHODS
We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online.
RESULTS
We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively.
CONCLUSION
TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.
PubMed: 38774264
DOI: 10.1016/j.bonr.2024.101772 -
Stem Cell Research Jun 2024Hypophosphatemic vitamin D-resistant rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. In this report,...
Establishing a human-induced pluripotent stem cell line SMUSHi005-A from a patient with hypophosphatemic vitamin D-resistant rickets carrying the PHEX c.1586-1586+1 delAG mutation.
Hypophosphatemic vitamin D-resistant rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. In this report, the SMUSHi005-A human induced pluripotent stem cell (hiPSC) line was successfully established from the PBMCs of a female patient carrying the PHEX mutation with c.1586-1586+1 delAG. The iPSC line has been confirmed to have a normal karyotype. The displayed cells clearly exhibit characteristics similar to embryonic stem cells, expressing pluripotency markers and demonstrating the ability to differentiate into three germ layers.
Topics: Humans; Induced Pluripotent Stem Cells; Female; PHEX Phosphate Regulating Neutral Endopeptidase; Mutation; Cell Line; Familial Hypophosphatemic Rickets; Cell Differentiation; Rickets, Hypophosphatemic; Vitamin D
PubMed: 38761687
DOI: 10.1016/j.scr.2024.103439 -
Poultry Science Apr 2024We aimed to determine the onset time of hypophosphatemic rickets and investigate the mechanism of motility impairment through adenosine triphosphate (ATP) production in...
Early manifestation of hypophosphatemic rickets in goslings: a potential role of insufficient muscular adenosine triphosphate in motility impairment of early P-deficient geese.
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 (R > 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.
PubMed: 38677064
DOI: 10.1016/j.psj.2024.103736 -
Children (Basel, Switzerland) Apr 2024This case report sheds light on the management of skeletal deformity in a young child with X-linked hypophosphatemia (XLH), emphasizing the significance of a timely...
This case report sheds light on the management of skeletal deformity in a young child with X-linked hypophosphatemia (XLH), emphasizing the significance of a timely orthotic intervention alongside pharmacological treatment, which is a strategy not frequently highlighted in the XLH literature. The patient, a 2-year-and-7-month-old female, presented with classic XLH symptoms, including short stature, pronounced genu varum, and hypophosphatemia, with deformities observed in both the coronal and sagittal planes of the femur and tibia. Despite initial reliance on pharmacotherapy, which proved insufficient for skeletal realignment, the integration of orthotic treatment at age 3 marked a pivotal turn in the management strategy. By the age of 5 years and 9 months, this combined approach yielded significant improvements: the deformities in the femur and tibia were notably corrected, tibial torsion was addressed, and enhanced limb alignment was achieved, as corroborated by radiographic evidence. This case underscores the effectiveness of orthotic intervention as a critical and underemphasized adjunct to pharmacological therapy in managing XLH in early childhood. It advocates for the early inclusion of orthotic measures to optimize treatment outcomes and expand the range of management strategies for limb deformities.
PubMed: 38671703
DOI: 10.3390/children11040487 -
Endocrinology, Diabetes & Metabolism... Apr 2024X-linked hypophosphatemic rickets (XLH), the most prevalent form of inherited hypophosphatemic rickets, is caused by loss-of-function mutations in the gene encoding...
SUMMARY
X-linked hypophosphatemic rickets (XLH), the most prevalent form of inherited hypophosphatemic rickets, is caused by loss-of-function mutations in the gene encoding phosphate-regulating endopeptidase homolog, X-linked (PHEX). This case series presents 14 cases of XLH from Gulf Cooperation Council (GCC) countries. The patients' medical history, biochemical and radiological investigative findings, as well as treatment responses and side effects from both conventional and burosumab therapy, are described. Cases were aged 2-40 years at diagnosis. There were two male cases and 12 female cases. All cases were treated with conventional therapy which resulted in a lack of improvement in or worsening of the clinical signs and symptoms of rickets or biochemical parameters. Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients' quality of life and adherence to treatment. In the 10 patients treated with burosumab, there was a marked improvement in the biochemical markers of rickets, with a mean increase in serum phosphate of +0.56 mmol/L and tubular maximum phosphate reabsorption (TmP) to glomerular filtration rate (GFR) ratio (TmP/GFR) of +0.39 mmol/L at 12 months compared to baseline. Furthermore, a mean decrease in serum alkaline phosphatase (ALP) of -80.80 IU/L and parathyroid hormone (PTH) of -63.61 pmol/L at 12 months compared to baseline was observed in these patients. Additionally, patients treated with burosumab reported reduced pain, muscle weakness, and fatigue as well as the ability to lead more physically active lives with no significant side effects of treatment.
LEARNING POINTS
Conventional therapy resulted in a suboptimal response, with a lack of improvement of clinical signs and symptoms. Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients' quality of life and adherence to treatment. Burosumab demonstrated marked improvements in the biochemical markers of rickets, in addition to reducing pain, muscle weakness, and fatigue. There were no significant side effects associated with burosumab therapy.
PubMed: 38614130
DOI: 10.1530/EDM-23-0098 -
International Journal of Molecular... Mar 2024X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset...
X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension. The median age was 44 years. Out of the total, seven (35%) subjects had a family history of hypertension. No statistically significant differences were found between both groups for nephrocalcinosis or hyperparathyroidism. Those with hypertension exhibited significantly higher levels of creatinine (1.08 ± 0.31 mg/dL vs. 0.78 ± 0.19 mg/dL; = 0.01) and LDL-C (133.33 ± 21.92 mg/dL vs. 107.27 ± 20.12 mg/dL, = 0.01). A total of 106 metabolites were identified. Acetylcarnitine ( = 0.03), pyruvate = (0.04), ethanolamine ( = 0.03), and butyric acid ( = 0.001) were significantly different between both groups. This study is the first to examine the metabolomics of hypertension in patients with XLH. We have identified significant changes in specific metabolites that shed new light on the potential mechanisms of hypertension in XLH patients. These findings could lead to new studies identifying associated biomarkers and developing new diagnostic approaches for XLH patients.
Topics: Adult; Humans; Familial Hypophosphatemic Rickets; Cross-Sectional Studies; Hypertension; Fibroblast Growth Factors
PubMed: 38542517
DOI: 10.3390/ijms25063545 -
Endocrinology and Metabolism (Seoul,... Apr 2024Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant... (Review)
Review
Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia (TIO), the most common form of acquired FGF23-related hypophosphatemic rickets/osteomalacia (FGF23rHR). After the identification of FGF23, many other inherited and acquired forms of FGF23rHR were reported. In this review article, the detailed features of each acquired FGF23rHR are discussed, including TIO, ectopic FGF23 syndrome with malignancy, fibrous dysplasia/McCune-Albright syndrome, Schimmelpenning-Feuerstein-Mims syndrome/cutaneous skeletal hypophosphatemia syndrome, intravenous iron preparation-induced FGF23rHR, alcohol consumption-induced FGF23rHR, and post-kidney transplantation hypophosphatemia. Then, an approach for the differential diagnosis and therapeutic options for each disorder are concisely introduced. Currently, the majority of endocrinologists might only consider TIO when encountering patients with acquired FGF23rHR; an adequate differential diagnosis can reduce medical costs and invasive procedures such as positron emission tomography/computed tomography and venous sampling to identify FGF23-producing tumors. Furthermore, some acquired FGF23rHRs, such as intravenous iron preparation/alcohol consumption-induced FGF23rHR, require only cessation of drugs or alcohol to achieve full recovery from osteomalacia.
Topics: Humans; Fibroblast Growth Factor-23; Osteomalacia; Fibroblast Growth Factors; Paraneoplastic Syndromes; Hypophosphatemia; Rickets, Hypophosphatemic; Neoplasms, Connective Tissue
PubMed: 38467164
DOI: 10.3803/EnM.2023.1908 -
Clinical Medicine Insights. Pediatrics 2024Hereditary Tyrosinemia Type 1 (HT1), a rare autosomal recessive metabolic disorder, arises from fumarylacetoacetate (FAH) enzyme deficiency, resulting in toxic...
BACKGROUND
Hereditary Tyrosinemia Type 1 (HT1), a rare autosomal recessive metabolic disorder, arises from fumarylacetoacetate (FAH) enzyme deficiency, resulting in toxic metabolite buildup. It manifests in acute, subacute, and chronic forms, with early diagnosis and Nitisinone treatment being vital.
OBJECTIVES
The study aims to highlight the different clinical presentations of Hereditary Tyrosinemia type 1 in a cohort of Pakistani children.
DESIGN
Retrospective observational study.
METHODOLOGY
All patients diagnosed with HT1 at Shifa International Hospital, Islamabad and Pak Emirates Military Hospital, Rawalpindi between 2010 and 2023 were included. Information was collected regarding age, gender, symptoms, physical signs, and laboratory results.
RESULTS
The study identified 6 cases of HT1. The average age at presentation was 8 months, with a mean delay in diagnosis of 26.8 months. Males were 4 (66.7%) and 2 (33.3%) were females. All patients had underlying liver disease presenting as abdominal distension with hepatosplenomegaly and accompanying growth failure. Four cases presented with rickets, 2 of which had hypophosphatemic rickets. Urine for succinylacetone was raised in all patients. Alpha fetoprotein was raised but hepatocellular carcinoma was diagnosed in 1 patient only. Low protein diet, and vitamin supplements were used for management. Five of the 6 patients died within 2 years of diagnosis.
CONCLUSION
Delayed referrals and unavailability of Nitisinone are the major challenges in diagnosing and treating HT1 in Pakistan.
PubMed: 38456192
DOI: 10.1177/11795565241236176 -
Frontiers in Pediatrics 2024Malformations of the lower limbs caused by hypophosphatemic rickets in older children are mostly complex, occurring on multiple planes without a single apex and showing...
OBJECTIVE
Malformations of the lower limbs caused by hypophosphatemic rickets in older children are mostly complex, occurring on multiple planes without a single apex and showing arcuate bending of the diaphysis combined with torsion deformity, and are difficult to correct. This study retrospectively investigated the effect of and indicators for multi-segment osteotomy with interlocking intramedullary nail fixation in the treatment of bony deformity caused by hypophosphatemic rickets.
METHODS
The clinical data of 21 hypophosphatemic rickets patients seen between August 2007 and March 2022 were collected. The age range of the patients at the first surgery was 11 years and 1 month old to 15 years and 3 months old, with an average age of 12 years and 8 months. There were 6 males and 15 females. All patients had abnormal alignment of their lower limbs, with 32 limbs having varus deformity and 10 limbs having valgus deformity.
RESULTS
A total of 67 surgeries were performed across the 21 patients, including 24 cases of femoral osteotomy with antegrade intramedullary nail fixation, 6 cases of femoral osteotomy with retrograde intramedullary nail fixation, and 20 cases of tibial osteotomy with interlocking intramedullary nail fixation. A total of 34 limbs eventually underwent interlocking intramedullary nail fixation, 9 with genu valgum and 25 with genu varus. All 21 patients were followed up for a period of 14∼96 months, with an average of 42.6 months. The ends of the osteotomies achieved bony union in 4-9 months (average 6.8 months), after which normal weight-bearing walking could be resumed. No infection, vascular or neurological complications, or nonunion occurred. During postoperative follow-up, the alignment the lower limbs passed through zone 1 in 13 limbs, zone 2 in 12 limbs, and zone 3 in 5 limbs. The overall rate of an excellent effect was 83.3%.
CONCLUSION
For lower limb deformity caused by hypophosphatemic rickets in older children, multi-segment osteotomy and strong fixation with interlocking intramedullary nails can achieve good correction outcomes.
PubMed: 38440186
DOI: 10.3389/fped.2024.1332531 -
BMC Oral Health Feb 2024X-linked hypophosphatemia (XLH) is a type of vitamin D-resistant rickets. It is the most common form of it and is related with oral health problems. This study aimed to...
BACKGROUND
X-linked hypophosphatemia (XLH) is a type of vitamin D-resistant rickets. It is the most common form of it and is related with oral health problems. This study aimed to analyze the OHRQoL of people suffering from XLH and measure physical oral health to confirm or refute evidence of reduced oral health.
METHODS
The German version of the Oral Health Impact Profile (OHIP-14G), was used to measure OHRQoL. All study participants underwent clinical examination, and oral health was scored using the Physical Oral Health Index (PhOX).
RESULTS
A total of 26 people participated in the study, of whom five were male and 21 were female. The average participant age was 40.9 ± 12.8 years. The OHIP-14G score was 14.3 (± 12.1; 95% CI: 9.37. 19.16) points (range 0-44 points). The PhOX score was 77.1 (± 9.9; 95% CI: 73.10-81.13) points (range 61-95 points).
CONCLUSIONS
The results of this study confirm that oral health and OHRQoL are both reduced in the studied cohort of people affected by XLH. Particular attention should be paid to perfect oral hygiene in people with XLH, as the impaired enamel mineralisation increases the risk of caries and thus also the occurrence of apical infections.
Topics: Humans; Male; Female; Adult; Middle Aged; Quality of Life; Oral Health; Familial Hypophosphatemic Rickets; Dental Caries; Surveys and Questionnaires
PubMed: 38383400
DOI: 10.1186/s12903-024-04028-9