BACKGROUND: X-linked hypophosphatemia is an orphan disease of genetic origin and multisystem involvement. It is characterized by a mutation of the PHEX gene which results in excess FGF23 production, with abnormal renal and intestinal phosphorus metabolism, hypophosphatemia and osteomalacia secondary to chronic renal excretion of phosphate. Clinical manifestations include hypophosphatemic rickets leading to growth abnormalities and osteomalacia, myopathy, bone pain and dental abscesses. The transition of these patients to adult life continues to pose challenges to health systems, medical practitioners, patients and families. For this reason, the aim of this consensus is to provide a set of recommendations to facilitate this process and ensure adequate management and follow-up, as well as the quality of life for patients with X-linked hypophosphatemia as they transition to adult life.
METHODS: Eight Latin American experts on the subject participated in the consensus and two of them were appointed as coordinators. The consensus work was done in accordance with the nominal group technique in 6 phases: (1) question standardization, (2) definition of the maximum number of choices, (3) production of individual solutions or answers, (4) individual question review, (5) analysis and synthesis of the information and (6) synchronic meetings for clarification and voting. An agreement was determined to exist with 80% votes in favor in three voting cycles.
CONCLUSIONS: Transition to adult life in patients with hypophosphatemia is a complex process that requires a comprehensive approach, taking into consideration medical interventions and associated care, but also the psychosocial components of adult life and the participation of multiple stakeholders to ensure a successful process. The consensus proposes a total of 33 recommendations based on the evidence and the knowledge and experience of the experts. The goal of the recommendations is to optimize the management of these patients during their transition to adulthood, bearing in mind the need for multidisciplinary management, as well as the most relevant medical and psychosocial factors in the region.

X连锁低磷性佝偻病是一种由于PHEX基因变异所致的骨骼和牙齿矿化障碍性X连锁显性遗传病，可累及骨骼、肌肉、牙齿等多系统多器官，致残率高。但症状缺乏特异性，难以与其他佝偻病鉴别。诊断需综合病史、症状和体征、生化检测、影像学检查、基因检测进行分析。本病尚无根治性治疗方法，临床多采用传统治疗（磷酸盐制剂和活性维生素D）、布罗索尤单抗、骨科治疗等。早期诊断、早期治疗可有效改善其预后及提高生活质量，患者需终生坚持多学科、多团队规范化治疗和随访。.

X-linked hypophosphataemia (XLH), the most common inherited form of rickets, is caused by a PHEX gene mutation that leads to excessive serum levels of fibroblast growth factor 23 (FGF23). This leads to clinical manifestations such as rickets, osteomalacia, pain, lower limb deformity and overall diminished quality of life. The overarching aims in the management of children with XLH are to improve quality of life by reducing overall burden of disease, optimise an individual\'s participation in daily activities and promote normal physical and psychological development. Burosumab, a monoclonal antibody targeting FGF23, has been shown to improve biochemistry, pain, function and radiological features of rickets in children with XLH and has transformed management of XLH around the world. Burosumab has been recently approved for clinical use in children with XLH in Australia. This manuscript outlines a clinical practice guideline for the use of burosumab in children with XLH to assist local clinicians, encourage consistency of management across Australia and suggest future directions for management and research. This guideline also strongly advocates for all patients with XLH to have multidisciplinary team involvement to ensure optimal care outcomes and highlights the need to consider other aspects of care for XLH in the era of burosumab, including transition to adult care and the effective coordination of care between local health-care providers and specialist services.

The objective of this project was to adapt to our setting following a systematic process based on the ADAPTE method the first clinical practice guidelines on X-linked hypophosphatemia (XLH) that were published in 2019.
The adaptation of the guidelines to our application and implementation setting was carried out in three phases -start-up, adaptation, and finalization- by a group of experts involved in the management of patients with XLH.
Following the original guide, the recommendations agreed by the group that elaborated the guidelines for diagnosis, frequency and scope of visits and specific follow-up in children and adults are presented. On the other hand, recommendations are established for both age groups with conventional treatment, as well as with burosumab in children or adults and those related to the controversial use of growth hormone in children. Suggestions are also proposed regarding the monitoring and management of musculoskeletal disorders and orthopedic treatment in children, dental health and hearing, and neurosurgical complications. Finally, a series of questions and areas are raised in order to deepen the possible future investigation.
These recommendations constitute the systematic adaptation to our setting of the first evidence-based clinical practice guide for the diagnosis and management of XLH and we hope that they can contribute to the adequate management of the disease.

暂无摘要。

The discovery of organ-network between bone and other organs revealed that organs other than bone are intimately involved in bone remodeling. Notably, control of bone remodeling by nervous system and control of phosphate and glucose metabolism by bone are areas of intense investigation. Moreover, metabolic diseases such as diabetes and COPD are shown to be involved in the pathogenesis of osteoporosis. Thus, osteoporosis is considered to be not just a local bone disease, but a manifestation of the whole body metabolism abnormality.

Rickets and osteomalacia are disorders of calcification characterized by defects of bone and cartilage mineralization during growth, and bone mineralization in adults, respectively. The specific x-ray findings including a cupping, flaring, and fraying of metaphysis and the elevation of the level of serum alkaline phosphatase are essential for the diagnosis of rickets. In addition, hypophosphatemia, hypocalcemia, and some symptoms including born deformity, spinal curvature, craniotabes, enlargement of the anterior fontanel, rachitic rosary, and joint swelling are also important. Clinicians need to consider the different normal ranges of the levels of serum alkaline phosphatase and phosphate depending on their patient\'s age when they diagnose their childhood patients. In contrast, the radiographic diagnosis of osteomalacia is difficult. The hypophosphatemia or hypocalcemia and the elevation of serum bone alkaline phosphatase are essential for the diagnosis of osteomalacia. Moreover, some clinical features including muscle weakness and bone pain, the decrease of bone density, and the finding of multiple uptake in bone scintigraphy or of the pseudofracture in bone x-ray study are also important. It is very useful for the differential diagnosis to measure the serum levels of 25-hydroxy vitamin D and fibroblast growth factor 23.

In developed countries, the continuing rise in the prevalence of hypertension, hyperlipidemia and diabetes has contributed to an overall increase in the incidence of both cardiovascular disease (CVD) and chronic kidney disease (CKD). The observation that even modest reductions in renal function correlate with increased CVD morbidity and mortality has led to the recognition that CKD is an independent risk factor for CVD. Conversely, there is a growing recognition that many pathologic conditions that contribute to CVD, including coronary artery disease, left ventricular hypertrophy and diastolic dysfunction, can accelerate the decline in renal function. In addition, physiologic mechanisms designed to compensate for reduced glomerular filtration rate including activation of the renin-angiotensin-aldosterone axis, the release of fibroblastic growth factor 23 and other mechanisms for calcium-phosphate homeostasis as well as and the pathophysiologic effects of uremic toxins can also directly contribute to CVD. The end result of the interaction between changes in pressure and volume overload and the physiologic compensation for the loss of function in both the heart and the kidney leads to accelerated decline in both organ systems. This complex physiologic and pathophysiologic interplay between the cardiovascular and renal systems is collectively referred to as the cardiorenal syndrome. The discussion which follows is aimed at outlining the pathophysiologic mechanisms linking advanced CKD (4 and 5) to the development of cardiac abnormalities which occur with unique frequency and severity in patients with severe impairment of renal function.

The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that mesenchymal cell-derived keratinocyte growth factor (KGF), a key stimulator of epithelial cell proliferation during wound healing, preferentially binds to collagens I, III, and VI. Binding is inhibited in a dose-dependent manner by denatured single collagen chains and collagen cyanogen bromide peptides. This interaction is saturable with dissociation constants of approximately 10(-8) to 10(-9) m and estimated molar ratios of up to three molecules of KGF bound to one molecule of triple helical collagen. Furthermore, collagen-bound KGF stimulated the proliferation of transformed keratinocyte or HaCaT cells. Ligand blotting of collagen-derived peptides points to a limited set of collagenous consensus sequences that bind KGF. By using synthetic collagen peptides, we defined the consensus sequence (Gly-Pro-Hyp)(n) as the collagen binding motif. We conclude that the preferential binding of KGF to the abundant collagens leads to a spatial pattern of bioavailable KGF that is dictated by the local organization of the collagenous extracellular matrix. The defined collagenous consensus peptide or its analogue may be useful in wound healing by increasing KGF bioactivity and thus modulating local epithelial remodeling and regeneration.