Materiały źródłowe

• #1 Rickets – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562285/

  Rickets is a condition characterized by a defect in mineralization of the epiphyseal plates. […] The acquired rickets (nutritional) is the most common cause of rickets worldwide. […] Vitamin-D, calcium, and phosphorus are the main factors that influence bone maturation and mineralization. Defective mineralization can lead to rickets and/or osteomalacia. Rickets is characterized by a defect in mineralization and the widening of the epiphyseal plates. Osteomalacia, however, is a defect in the mineralization of the bone matrix. […] Vitamin D deficiency is, by far, the most common cause of nutritional rickets. […] Based on the biochemical profile, rickets can be classified into calcipenic, phosphopenic, and rickets due to inhibited mineralization. […] Deficiency of calcium results in calcipenic rickets, and vitamin D deficiency is the most common etiology for calcipenic rickets.

• #2

  https://www.orthobullets.com/basic-science/9031/rickets

  Rickets is a metabolic bone disease caused by a defect in mineralization of osteoid matrix caused by inadequate calcium and phosphate that occurs prior to closure of the physes. […] Vitamin D and PTH play an important role in calcium homeostasis. […] Disruption of calcium/phosphate homeostasis leads to poor calcification of cartilage matrix of growing long bones. […] This occurs at the zone of provisional calcification and leads to increased physeal width and cortical thinning/bowing. […] Rickets is known as osteomalacia if it occurs after physeal closure. […] It can be congenital or acquired. […] Pathophysiology of Vitamin D-deficient rickets involves low Vitamin D levels leading to decreased intestinal absorption of calcium, which results in low calcium levels and a compensatory increase in PTH and bone resorption.

• #3 Overview of rickets in children – UpToDate

  https://www.uptodate.com/contents/overview-of-rickets-in-children

  INTRODUCTION […] Normal bone growth and mineralization require adequate calcium and phosphate, the two major nutritional elements that constitute the crystalline component of bone. Deficient mineralization can result in rickets and/or osteomalacia. Rickets refers to deficient mineralization at the growth plate, as well as architectural disruption of this structure. Osteomalacia refers to impaired mineralization of the bone matrix. Rickets and osteomalacia usually occur together as long as the growth plates are open; only osteomalacia occurs after the growth plates have fused. […] An overview of the pathogenesis, clinical presentation, and the differential diagnosis of rickets is presented here. […] […] TYPES OF RICKETS […] Mineralization defects are classified according to the predominant mineral deficiency:

• #4 Rickets | PPT

  https://www.slideshare.net/slideshow/rickets-87156151/87156151

  Rickets is a disease of infancy and childhood due to disturbances in calcium and phosphate metabolism which results in defective mineralization of growing bones before fusion of epiphyses. […] The characteristic pathological changes in rickets arise from the inability to calcify the intercellular matrix in the deeper layers of the physis. […] Vitamin D = increase the absorption of calcium from intestine PTH = mobilizes calcium from bone and increases urinary excretion of phosphate Calcitonin = inhibits bone resorption. […] Rickets is caused by a lack of vitamin D, calcium, or phosphate which leads to softening and weakening of the bones due to defective mineralization of bone matrix. […] It results from vitamin D deficiency which prevents proper absorption of calcium and phosphate from the diet.

• #5 Rickets – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562285/

  Phosphopenic rickets, on the other hand, is caused by conditions that cause chronic low serum phosphate levels, either from impaired intestinal absorption or, more commonly, from increased renal loss. […] Inhibited mineralization rickets occurs when there is a defect in growth plate mineralization in the presence of normal calcium and phosphate concentrations. […] Any defect in osteoid mineralization may cause rickets. […] Low serum calcium, either from its low intake or from vitamin D deficiency, causes a compensatory increase in the PTH, which subsequently causes hypophosphatemia. […] Growth plate abnormalities occur due to reduced vascular invasion with decreased chondroblast and osteoclast activity.

• #6 An Overview of Rickets in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7335963/

  Rickets can be classified into 2 major groups based on phosphate or calcium levels: phosphopenic and calcipenic. […] In rickets, this process is hampered and results in amassing of osteoid beneath the growth plate leading to softness in the bone over a gradual period of time. […] In phosphopenic/hypophosphatemic rickets, the defect usually results from increased renal excretion of phosphate. […] Calcipenic rickets, as the name suggests, happens primarily because of a lack of calcium, which is most commonly due to a low availability or defective functioning of vitamin D in the body. […] The common pathway in the development of rickets in both calcipenic and phosphopenic forms is reduced phosphate concentration. […] Hypocalcemia, hypophosphatemia, and PTH stimulate the synthesis of 1,25-dihydroxy vitamin D.

• #7 Overview of rickets in children – UpToDate

  https://www.uptodate.com/contents/overview-of-rickets-in-children

  • Calcipenic rickets is caused by calcium deficiency, which usually is due to insufficient intake of vitamin D or failure to metabolize dietary vitamin D into its active form. In some cases, it is caused by insufficient intake or absorption of calcium in the setting of normal vitamin D levels. Calcipenic rickets may be associated with low serum calcium levels but also occurs in the setting of normocalcemia. […] • Phosphopenic rickets is characterized by low serum levels of phosphorus, usually caused by renal phosphate wasting and, less commonly, by nutritional phosphorus deficiency.

• #8 Rickets in Children: An Update

  https://www.mdpi.com/2227-9059/9/7/738

  Rickets refers to a deficient mineralization of the growth plate cartilage, predominantly affecting longer bones. […] Although recent studies suggest hypophosphatemia as the leading alteration, rickets is classically divided into two categories: calcipenic rickets and phosphopenic rickets. […] Based on the biochemical predominant abnormalities, rickets was typically classified as calcipenic or phosphopenic, although evidence suggests hypophosphatemia as the leading pathogenetic denominator of all forms. […] Hypophosphatemia is directly responsible for the reduced apoptosis of the growth plate’s hypertrophic chondrocytes and, consequently, for the development of clinical and radiological rachitic changes. Thus, despite the different mechanisms, hypophosphatemia can be considered the common denominator of both calcipenic and phosphopenic rickets.

• #9 Rickets: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/985510-overview

  Rickets is a disease of growing bone that is unique to children and adolescents. It is caused by a failure of osteoid to calcify in a growing person. […] Vitamin D deficiency rickets occurs when the metabolites of vitamin D are deficient. Less commonly, a dietary deficiency of calcium or phosphorus may also produce rickets. […] During the Industrial Revolution, rickets appeared in epidemic form in temperate zones where the pollution from factories blocked the suns ultraviolet rays. Thus, rickets was probably the first childhood disease caused by environmental pollution. […] Rickets may lead to skeletal deformity and short stature. In females, pelvic distortion from rickets may cause problems with childbirth later in life. Severe rickets has been associated with respiratory failure in children.

• #10 Rickets: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/985510-overview

  Cholecalciferol (ie, vitamin D-3) is formed in the skin from 5-dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps. The first hydroxylation occurs at position 25 in the liver, producing calcidiol (25-hydroxycholecalciferol), which circulates in the plasma as the most abundant of the vitamin D metabolites and is thought to be a good indicator of overall vitamin D status. […] The second hydroxylation step occurs in the kidney at the 1 position, where it undergoes hydroxylation to the active metabolite calcitriol (1,25-dihydroxycholecalciferol). This cholecalciferol, which circulates in the bloodstream in minute amounts, is not technically a vitamin but a hormone. […] Calcitriol acts at 3 known sites to tightly regulate calcium metabolism: (1) it promotes absorption of calcium and phosphorus from the intestine; (2) it increases reabsorption of phosphate in the kidney; and, (3) it acts on bone to release calcium and phosphate. Calcitriol may also directly facilitate calcification.

• #11

  https://www.orthobullets.com/basic-science/9031/rickets

  Bone resorption leads to increased alkaline phosphatase levels. […] In Vitamin D-dependent rickets, type I results from autosomal recessive mutation in renal 25-(OH)-1-hydroxylase, preventing conversion of inactive form of vitamin D to active form, leading to decreased calcitriol. […] Type II results from autosomal recessive mutation in intracellular receptor for 1,25-(OH)2-vitamin D, leading to increased calcitriol.

• #12 Rickets: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/985510-overview

  This increase of calcium and phosphorus in extracellular fluid, in turn, leads to the calcification of osteoid, primarily at the metaphyseal growing ends of bones but also throughout all osteoid in the skeleton. […] In the vitamin D deficiency state, hypocalcemia develops, which stimulates excess secretion of parathyroid hormone. In turn, renal phosphorus loss is enhanced, further reducing deposition of calcium in the bone. […] Excess parathyroid hormone also produces changes in the bone similar to those occurring in hyperparathyroidism. Early in the course of rickets, the calcium concentration in the serum decreases. […] Studies have noted that disorders of increased fibroblast growth factor 23 (FGF-23) function are associated with rickets.

• #13 Rickets: Not a Disease of the Past | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/0815/p619.html

  Rickets develops when growing bones fail to mineralize. […] Vitamin D-dependent rickets, type I results from abnormalities in the gene coding for 25(OH)D3-1–hydroxylase, and type II results from defective vitamin D receptors. […] A disease that occurs during childhood, rickets is the failure of growing bone to mineralize. Many skeletal and radiographic changes can occur because of the lack of calcified osteoid and the buildup of unossified cartilage. Proper bone formation requires a complex interplay of several organs and chemicals, and vitamin D deserves special mention because any disturbance in its production, absorption, or metabolism is paramount in the development of rickets. […] Nutritional rickets results from inadequate sunlight exposure or inadequate intake of dietary vitamin D, calcium, or phosphorus.

• #14 Rickets: Not a Disease of the Past | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/0815/p619.html

  Vitamin D-dependent rickets, type I is secondary to a defect in the gene that codes for the production of renal 25(OH)D31–hydroxylase. Vitamin D-dependent rickets, type II is a rare autosomal disorder caused by mutations in the vitamin D receptor. […] Rickets refractory to vitamin D treatment may be caused by the most common heritable form, known as vitamin D-resistant rickets or familial hypophosphatemic rickets. […] Various medical conditions and medications can cause rickets. In rickets secondary to malignancy, the most common pathophysiology is tumor secretion of a renal phosphate-wasting factor and impaired calcitriol production. Rickets caused by renal disease (renal osteodystrophy) is caused by disturbances in calcium and phosphorus regulation and calcitriol production. Malabsorption syndromes such as celiac disease and cystic fibrosis can cause vitamin D deficiency.

• #15 Hypophosphatemic Rickets: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/922305-overview

  Hypophosphatemic rickets is a form of rickets that is characterized by low serum phosphate levels and resistance to treatment with ultraviolet radiation or vitamin D ingestion. […] Study of these refractory cases revealed low serum phosphate concentration as a common factor. Familial occurrence of this condition led to the diagnosis of familial hypophosphatemic rickets. […] With advances in the understanding of the genetic basis of familial hypophosphatemic rickets, the term X-linked hypophosphatemic rickets has become more commonly used. X-linked hypophosphatemia (XLH) is a dominant disorder and accounts for more than 80% of all familial hypophosphatemia. XLH is considered to be a systemic disorder, from mutation of the phosphate-regulating gene homologous to endopeptidases on the X chromosome (PHEX).

• #16 An Overview of Rickets in Children

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7335963/

  The main defect in these forms of rickets is the increased loss of phosphate through the urine. […] The term renal rickets is usually restricted to those with chronic kidney disease. […] Chronic kidney disease results in the deficiency of the enzyme 1 alpha-hydroxylase, which decreases the production of 1,25 hydroxy vitamin D (calcitriol). […] An important recent development is the introduction of burosumab, a human monoclonal antibody against FGF-23 that has been shown to be effective in children with X-linked hypophosphatemia.

• #17 Hereditary hypophosphatemic rickets: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hereditary-hypophosphatemic-rickets/

  Hereditary hypophosphatemic rickets can result from mutations in several genes. Mutations in the PHEX gene, which are responsible for X-linked hypophosphatemic rickets, occur most frequently. […] Hereditary hypophosphatemic rickets is characterized by a phosphate imbalance in the body. Among its many functions, phosphate plays a critical role in the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys. The kidneys normally excrete excess phosphate in urine, and they reabsorb this mineral into the bloodstream when more is needed. However, in people with hereditary hypophosphatemic rickets, the kidneys cannot reabsorb phosphate effectively and too much of this mineral is excreted from the body in urine. As a result, not enough phosphate is available in the bloodstream to participate in normal bone development and maintenance.

• #18 Hypophosphatemic Rickets: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/922305-overview

  FGF-23 requires heparin and Klotho for binding to the proximal tubule to stimulate phosphaturia. […] The pathogenesis of hypophosphatemic rickets is clear; phosphate wasting at the proximal tubule level is the basis of the affected individual’s inability to establish normal ossification. This phenomenon is secondary to defective regulation of the sodium-phosphate cotransporter in the epithelial cell brush border. […] Inadequate levels of inorganic phosphate impair the function of mature osteoblasts (ie, bone matrix ossification), because formation of mature bone involves the precipitation of hydroxyapatite [3-Ca3 (PO4)2: Ca(OH)2] crystals. […] Although much has been learned about the etiology of hypophosphatemic rickets, a great deal more remains undiscovered.

• #19 Frontiers | Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology

  https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1383681/full

  In this position paper, the various forms of rickets are subdivided into four major categories based on the main pathogenesis, such as nutritional, hereditary, non-hereditary hypophosphatemic, and other forms. […] Hypophosphatemic rickets include some disorders that may be associated with overproduction of fibroblast growth factor 23 (FGF23), namely FGF23-dependent forms, and disorders associated with a primary renal defect with normal concentrations of circulating FGF23, namely FGF23-independent forms. […] The excessive production of FGF23 reduces tubular phosphate reabsorption and 1α-hydroxylase activity and stimulates renal 24-hydroxylase activity. […] The reduced TmP/GFR ratio found in patients with hypophosphatemic rickets is due to an overproduction or reduced degradation of fibroblast growth factor 23 (FGF23).

• #20 Function of PHEX mutations p.Glu145* and p.Trp749Arg in families with X-linked hypophosphatemic rickets by the negative regulation mechanism on FGF23 promoter transcription | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04969-5

  X-linked hypophosphatemic rickets (XLH) is characterized by increased circulating fibroblast growth factor 23 (FGF23) concentration caused by PHEX (NM_000444.5) mutations. […] By phenotypic-genetic linkage analysis, two PHEX pathogenic mutations were found in two XLH families: c.433GT, p.Glu145* in exon 4 and c.2245TC, p.Trp749Arg in exon 22. […] The regulatory mechanism between PHEX and FGF23 is still unclear, but we found that PHEX is a direct transcriptional inhibitor of FGF23 and affects the expression of FGF23. […] This study verified the pathogenicity of the two variants and revealed the possible regulatory mechanism between PHEX and FGF23. […] The purpose of this study was to prove the pathogenicity of two variants of the PHEX gene found in a previous study. It has been preliminarily confirmed that p.Glu145* and p.Trp749Arg are pathogenic variants, and the molecular mechanism of XLH has been suggested. Interestingly, this study found that PHEX negatively regulates the transcription of FGF23 promoter, which provides a new explanation for the regulatory mechanism between PHEX and FGF23.

• #21 Function of PHEX mutations p.Glu145* and p.Trp749Arg in families with X-linked hypophosphatemic rickets by the negative regulation mechanism on FGF23 promoter transcription | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04969-5

  PHEX pathogenicity is a complex pathological process. […] The two variants p.Glu145* and p.Trp749Arg lead to the decline of PHEX protein function. […] In this study, we have identified two new variants in the Chinese population, along with their cellular function, and tried to clarify the regulatory mechanism between PHEX and FGF23.

• #22 Hereditary hypophosphataemic rickets — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/hereditary-hypophosphataemic-rickets/

  Hereditary hypophosphataemic rickets is a group of genetic conditions in which pathogenic variants in genes encoding hormones, receptors and ion transporters involved in phosphate handling cause lifelong hypophosphataemia and associated clinical manifestations. […] Incompletely understood, but it is established that loss-of-function variants in the PHEX gene are associated with elevated expression of FGF 23, primarily in osteocytes, leading to renal phosphate wasting, reduced activation of 25 OH vitamin D to 1,25 di OH D and impaired bone mineralisation. […] Gain-of-function variants lead to stabilisation of full-length (32 kDa) FGF 23 by substituting arginine with glutamine or tryptophan within the RXXR subtilisin-like proprotein convertase (SPC) cleavage site. This leads to enhanced FGF 23 activity and consequent renal phosphate wasting, hypophosphataemia and impaired bone mineralisation.

• #23

  https://link.springer.com/article/10.1007/s00467-021-05328-w

  Rickets is a disease of the growing child arising from alterations in calcium and phosphate homeostasis resulting in impaired apoptosis of hypertrophic chondrocytes in the growth plate. […] The latter are due to mutations in genes involved in vitamin D metabolism or action, renal phosphate reabsorption, or synthesis, or degradation of the phosphaturic hormone fibroblast growth factor 23 (FGF23). […] Apoptosis of hypertrophic chondrocytes is induced by extracellular phosphate via phosphorylation of mitogen-activated protein kinase (MAPK) pathway intermediates and downstream inhibition of the caspase-9-dependent mitochondrial apoptotic pathway. Thus, reduction in ambient phosphate availability to the chondrocyte, which is common to all forms of rickets, seems to be central to the impaired apoptosis.

• #24

  https://link.springer.com/article/10.1007/s00467-021-05328-w

  Recent data provides strong evidence that the real culprit is insufficient availability of phosphate which is a prerequisite for terminal differentiation of growth plate chondrocytes. […] Studies in various animal models of rickets show that reduced concentrations of extracellular phosphate impair caspase-9-mediated apoptosis of hypertrophic chondrocytes, causing the characteristic rachitic changes. […] The underlying causes of hypophosphatemia are the basis of the diagnostic algorithm given in Fig. 6 which is described below. […] Calcipenic rickets results from impaired calcium availability, which is either due to reduced calcium intake and/or vitamin D deficiency (nutritional rickets) or impaired action of 1,25(OH)2D (vitamin D-dependent rickets) (VDRR). […] In general, the reduced availability of calcium results in a tendency toward lower serum Ca which stimulates PTH synthesis, in order to maintain normal serum Ca++ levels by enhancing renal 1,25(OH)2D synthesis and, thereby, intestinal calcium absorption.

• #25

  https://www.jci.org/articles/view/29449

  Vitamin D deficiency causes global poor mineralization of the skeleton. Clinical and radiological bone manifestations predominate in areas of rapid bone growth, including the long bone epiphyses and the costochondral junctions. […] Vitamin D deficiency in utero and during the first year of life has devastating consequences and may imprint on the child’s life chronic diseases that will shorten his/her life span. […] Vitamin D deficiency should be immediately treated with at least 1,000 IU of vitamin D2 or vitamin D3/day for the first week of life.

• #26 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Rickets-Symptoms.aspx

  Vitamin D has a major impact on skeletal growth and health. Any disturbance in its production, absorption, or metabolism is paramount in the development of rickets. […] Moreover, insufficient vitamin D concentrations often result in decreased intestinal absorption of calcium. […] Even a slight decrease in serum calcium concentrations that can ensue stimulates the secretion of parathyroid hormone, which, in turn, mobilizes calcium and phosphorus from the bones in order to restore serum concentrations to normal levels. When a mineral deficiency occurs at the growth plate, growth slows and bone age is retarded. […] Nutritional rickets results either from insufficient sunlight exposure or inadequate intake of dietary vitamin D, calcium, or phosphorus. This type of disease continues to be problematic among infants in many communities, namely among those who are exclusively breastfed.

• #27 Hereditary hypophosphatemic rickets and tumor-induced osteomalacia – UpToDate

  https://www.uptodate.com/contents/hereditary-hypophosphatemic-rickets-and-tumor-induced-osteomalacia

  Hereditary hypophosphatemic rickets refers to several inherited disorders characterized by renal phosphate wasting, the most common of which is X-linked hypophosphatemia (XLH). An acquired disorder, tumor-induced osteomalacia (TIO), has similar clinical manifestations to the inherited disorders. […] X-linked hypophosphatemia (XLH), other inherited forms of fibroblast growth factor 23 (FGF23)-mediated hypophosphatemic rickets, and tumor-induced osteomalacia (TIO) are all characterized by hypophosphatemia, normal serum levels of calcium, and either normal or modestly elevated levels of parathyroid hormone (PTH). These disorders have high or inappropriately normal circulating levels of FGF23, a circulating hormone that causes renal phosphate wasting and is a common final pathway. The elevated FGF23 activity is the basis for treatment with the anti-FGF23 monoclonal antibody burosumab.

• #28 Hypophosphatemic Rickets – Pediatrics – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/pediatrics/congenital-renal-transport-abnormalities/hypophosphatemic-rickets

  Hypophosphatemic rickets is a genetic disorder characterized by hypophosphatemia, defective intestinal absorption of calcium, and rickets or osteomalacia unresponsive to vitamin D. […] The observed abnormality is decreased proximal renal tubular resorption of phosphate, resulting in renal phosphate wasting and hypophosphatemia. This defect is due to circulating factors called phosphatonins. The principle phosphatonin in hereditary hypophosphatemic rickets is fibroblast growth factor-23 (FGF-23). Decreased intestinal calcium and phosphate absorption also occurs. Deficient bone mineralization is due to low phosphate levels and osteoblast dysfunction rather than to the low calcium and elevated parathyroid hormone (PTH) levels as in calcipenic rickets. […] Tumor-induced osteomalacia is a nongenetic cause of hypophosphatemia with rickets in children. This disorder is caused by a paraneoplastic phenomenon in which ectopic fibroblast growth factor-23 (FGF-23) is produced, leading to phosphaturia and complications similar to hereditary hypophosphatemic rickets. […] Decreased renal resorption of phosphate results in renal phosphate wasting and hypophosphatemia. There is deficient bone mineralization due to low phosphate levels and osteoblast dysfunction.

• #29 Rickets in renal tubular acidosis: A clinical appraisal

  https://www.probiologists.com/article/rickets-in-renal-tubular-acidosis-a-clinical-appraisal

  Rickets, a metabolic disease restricted to an age group before epiphyseal growth plate fusion, and is diagnosed by typical skeletal deformities and characteristic radiological features. […] Renal tubular acidosis is an important cause of rickets, particularly resistant rickets, as the diagnosis is often missed initially and the patients are being wrongly treated with other agents without any benefit. […] Early diagnosis and proper management of renal tubular acidosis leads to complete clinical and radiological recovery in patients presenting with rickets secondary to renal tubular acidosis. […] Rickets in RTA is multifactorial. Systemic acidosis is associated with defective mineralization of the cartilages and bones due to increased solubility of the mineral phase. […] In addition, pRTA itself may be associated with phosphaturia and low renal 1-hydroxylase activity, which leads to impaired conversion of 25-hydroxy vitamin D to calcitriol (1, 25-dihydroxy vitamin D), the active form of vitamin D.

• #30 Hypophosphatemic rickets: pathogenesis, diagnosis and treatment | Kulikova | Obesity and metabolism

  https://www.omet-endojournals.ru/omet/article/view/9672?locale=en_US

  Hypophosphatemic rickets (HR) – a group of diseases characterized by the development of ricketic changes in bone tissue due to increased excretion of phosphorus from the body. […] Currently, more than 10 candidate genes are known, the defects in which lead to the development of congenital forms of GFR. Genetic diagnostics of the HR is of great importance for determining the form of the HR, and for carrying out genetic counseling of families when planning pregnancy.

• #31 Hereditary hypophosphataemic rickets — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/hereditary-hypophosphataemic-rickets/

  Variants are thought to result in non-functional DMP-1 protein, causing impaired osteocyte maturation and associated excess FGF 23 secretion. […] It is hypothesised that ENPP1 may regulate osteoblast differentiation, meaning that variants may affect osteocyte differentiation (osteocytes being derived from osteoblasts) and lead to excessive FGF 23 secretion, as occurs in ARHR 1. […] Variants in the conserved C terminal domain of FAM20C are usually lethal. However, some variants are compatible with life and cause a phenotype with craniofacial anomalies, osteosclerosis and in one reported case, high FGF 23 levels. […] Homozygous or compound heterozygous inactivating variants in SLC34A3 lead to excess renal phosphate losses with elevated 1,25 di OH D levels and hypercalciuria secondary to this, leading to nephrolithiasis and distinguishing HHRH from conditions in which the primary anomaly is excess FGF 23 secretion, such as XLH.

• #32 Hereditary hypophosphataemic rickets — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/hereditary-hypophosphataemic-rickets/

  KL gene translocation leading to enhanced FGF 23 signalling (klotho being the FGF 23 co-receptor in kidney and parathyroid). This leads to renal phosphate wasting and hyperparathyroidism as well as elevated FGF 23 levels, which would not be predicted to be part of the phenotype. This suggests that klotho may have an additional role in regulating FGF 23 secretion. […] The phenotype is renal Fanconi syndrome with hypophosphataemic rickets and severe short stature and, as in HHRH, hypercalciuria and elevated 1,25 di OH D levels.

• #33 Rickets Types and Treatment with Vitamin D and Analogues

  https://www.mdpi.com/2072-6643/16/3/416

  From an etiopathogenetic perspective, hypophosphatemic rickets can be subdivided into forms based on reduced phosphate intake or excessive renal phosphate loss, which are associated with hypophosphaturia and hyperphosphaturia, respectively. […] Rickets therapy is based on vitamin D and calcium supplementation, plus phosphate when necessary. […] The treatment of genetic vitamin D-dependent rickets must be continued for life, with patient tailored doses. […] The mechanism of action of this neutralizing antibody is the inactivation of serum FGF23 by enhancing renal phosphate reabsorption and increasing its circulating concentrations. […] Overall, Burosumab treatment has proved to be more effective than conventional therapy in improving rickets, growth, lower limb deformities, and walking in children with XLH from 1 to 12 years of age.

• #34 Rickets – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rickets/symptoms-causes/syc-20351943

  Factors that can increase a child’s risk of rickets include: Darker skin pigmentation, Mother’s vitamin D deficiency during pregnancy, Northern latitudes, Premature birth, Medicines, Exclusive breastfeeding. […] If not treated, rickets can lead to: Failure to grow, Bone deformities, Dental defects, Seizures. […] Exposure to sunlight provides the best source of vitamin D. During most seasons, 10 to 15 minutes of exposure to the sun near midday is enough. But if you have brown or Black skin, if it’s winter, or if you live in northern latitudes, you might not be able to get enough vitamin D from sun exposure. […] To prevent rickets, make sure your child eats foods that contain vitamin D naturally fatty fish such as salmon and tuna, fish oil, and egg yolks or that have been fortified with vitamin D.

• #35 Rickets: Definition, Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/22459-rickets

  Inherited rickets: Several genetic diseases interfere with how your childs body absorbs vitamin D. Other genetic conditions affect how your body handles phosphorus and also cause rickets. These types of disorders are rare. […] Yes, most cases of rickets (especially nutritional rickets) are curable when caught early. In most cases, changes to diet, added vitamin supplements and more sunlight exposure are enough to cure this disease. […] For inherited cases of rickets, there are several treatment options depending on the genetic disorder in question. […] While rickets is a treatable and often curable disease, its important to treat it as soon as possible. When not treated, milder cases of rickets can result in long-term bone that can keep bones from growing properly. Severe cases that arent treated can lead to seizures, heart damage and death.

• #36 Frontiers | Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology

  https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1383681/full

  Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. […] Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. […] Rickets is a skeletal disease characterized by deficient mineralization of growth plates and bone matrix (osteomalacia) associated with low concentrations of calcium and/or phosphate in the blood. […] Treatment and management of rickets should be targeted on the pathogenesis and both are strictly connected with the diagnosis.

• #37 Rickets: Symptoms, Diagnosis, and Treatments

  https://www.healthline.com/health/rickets

  Rickets is a skeletal disorder thats caused by a lack of vitamin D, calcium, or phosphate. These nutrients are important for the development of strong, healthy bones. […] A vitamin D deficiency makes it difficult for your body to maintain sufficient levels of calcium and phosphate. When this occurs, your body produces hormones that cause calcium and phosphate to be released from your bones. When your bones lack these minerals, they become weak and soft. […] Treatment for rickets focuses on replacing the missing vitamin or mineral in the body. This will eliminate most of the symptoms associated with rickets. […] For hereditary rickets, a combination of phosphate supplements and high levels of a special form of vitamin D are required to treat the disease. […] Increasing vitamin D, calcium, and phosphate levels will help correct the disorder. Most children with rickets see improvements in about one week. […] Rickets can also be prevented with moderate sun exposure.

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