Clinical practice recommendations for the diagnosis and treatment of X-linked hypophosphatemia: A consensus based on the ADAPTE method

González‐Lamuño, Domingo; Rodríguez, Ana Lorente; Yanes, María I. Luis; Barrio, Silvia Marín-del; Díaz-Guerra, Guillermo Martínez; Peris, Pilar

doi:10.1016/j.medcle.2021.07.026

Cited by 6 publications

(27 citation statements)

References 36 publications

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“…(38,42,44) Nevertheless, XLH should be differentiated from non-selective causes of renal phosphate wasting (ie, Fanconi syndrome) that present with other distinctive features such as bicarbonate and uric acid wasting, glucosuria, aminoaciduria, and low-molecularweight proteinuria. (12,13,19,22,23) Alkaline phosphatase, a marker of bone turnover, is elevated in association with rickets and osteomalacia. Because bonespecific ALP constitutes $90% of total ALP in children and only $50% in adults, total ALP may be used for children, whereas bone-specific ALP is recommended for adults.…”

Section: Biochemical Featuresmentioning

confidence: 99%

“…The generally recommended starting doses in children are 20-60 mg/kg body weight of elemental phosphorus given 4-6 times daily, and 20-40 ng/kg body weight of calcitriol given in two doses per day or 30-50 ng/kg body weight of alfacacidol given once daily. (12,13,19,22,23,84) Abbreviation: APAC = Asia-Pacific; GRADE = Grading of Recommendations, Assessment, Development, and Evaluations; XLH = X-linked hypophosphatemia.…”

Section: Conventional Therapymentioning

confidence: 99%

“…(52,79) Hence, contemporary guidelines recommend initiating or continuing combination therapy with oral phosphate and active vitamin D only in symptomatic adults, specifically those with dental problems, musculoskeletal pain, pseudofractures, elevated ALP, or planned orthopedic or dental surgery. (12,13,22) In general, the recommended doses of conventional treatment for adults are 750-2000 mg of elemental phosphorus divided into 2-4 doses daily, and 0.50-0.75 μg of calcitriol or 0.75-1.5 μg of alfacacidol daily. (12,13,22,23) Despite the clinical benefits of conventional treatment, the multiple daily doses required may disrupt routine activities and become burdensome to patients.…”

Section: Conventional Therapymentioning

confidence: 99%

“…Conventional therapy must be discontinued 2 weeks before burosumab therapy, and the child should have a serum phosphate level below the lower end of the age-adjusted reference range. (12,13,19,(21)(22)(23) Among adults, the clinical benefits of burosumab therapy over placebo have also been illustrated by RCTs. (50,51,67,92) In a large-scale, international, phase 3 RCT among adults with XLH (N = 134), the burosumab group had a significantly higher proportion of subjects achieving a normalization in serum phosphate versus the placebo group (94.1% versus 7.6%, p < 0.001) at 24 weeks, as well as greater improvements in fracture/ pseudofracture healing, other biochemical parameters, and patient-reported outcomes (PROs).…”

Section: Annually Based On Availability Of Resourcesmentioning

confidence: 99%

“…(102) No prior consensus or strong recommendation has been established regarding conventional therapy for pregnant or lactating patients with XLH. (12,13,22,23) Nevertheless, pregnancy and lactation are critical periods for bone health, as bone mineralization disorders may also exacerbate during pregnancy. (103) Therefore, intensification of monitoring under these circumstances is essential.…”

Section: Pregnancy and Lactationmentioning

confidence: 99%

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Asia‐Pacific Consensus Recommendations on X‐Linked Hypophosphatemia: Diagnosis, Multidisciplinary Management, and Transition From Pediatric to Adult Care

Munns

Yoo

et al. 2023

JBMR Plus

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X-linked hypophosphatemia (XLH) is a rare, inherited, multisystem disorder characterized by hypophosphatemia that occurs secondary to renal phosphate wasting. Mutations in PHEX gene (located at Xp22.1) in XLH alter bone mineral metabolism, resulting in diverse skeletal, dental, and other extraskeletal abnormalities that become evident in early childhood and persist into adolescence and adult life. XLH impacts physical function, mobility, and quality of life, and is associated with substantial socioeconomic burden and health care resource utilization. As the burden of illness varies with age, an appropriate transition of care from childhood and adolescence to adulthood is necessary to meet growth-related changes and minimize long-term sequelae of the condition. Previous XLH guidelines that encompassed transition of care have focused on Western experience. Regional differences in resource availability warrant tailoring of recommendations to the Asia-Pacific (APAC) context. Hence, a core expert panel of 15 pediatric and adult endocrinologists from nine countries/regions across APAC convened to formulate evidence-based recommendations for optimizing XLH care. A comprehensive literature search on PubMed using MeSH and free-text terms relevant to predetermined clinical questions on diagnosis, multidisciplinary management, and transition of care of XLH revealed 2171 abstracts. The abstracts were reviewed independently by two authors to shortlist a final of 164 articles. A total of 92 full-text articles were finally selected for data extraction and drafting the consensus statements. Sixteen guiding statements were developed based on review of evidence and real-world clinical experience. The GRADE criteria were used to appraise the quality of evidence supporting the statements. Subsequently, a DelphiThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Biochemical Featuresmentioning

confidence: 99%

Section: Conventional Therapymentioning

confidence: 99%

Section: Conventional Therapymentioning

confidence: 99%

Section: Annually Based On Availability Of Resourcesmentioning

confidence: 99%

Section: Pregnancy and Lactationmentioning

confidence: 99%

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Asia‐Pacific Consensus Recommendations on X‐Linked Hypophosphatemia: Diagnosis, Multidisciplinary Management, and Transition From Pediatric to Adult Care

Munns

Yoo

et al. 2023

JBMR Plus

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Latin-American consensus on the transition into adult life of patients with X-linked hypophosphatemia

Kastelic,

Roman-González,

De Paula Colares Neto

et al. 2023

Endocrine

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Introduction 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. Materials and 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. Results and Discussion 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.

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The International X-Linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data

Ariceta,

Beck-Nielsen,

Boot

et al. 2023

Orphanet J Rare Dis

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Background X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient’s lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry. Results The International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately − 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH. Conclusion The data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.

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Clinical practice recommendations for the diagnosis and treatment of X-linked hypophosphatemia: A consensus based on the ADAPTE method

Cited by 6 publications

References 36 publications

Asia‐Pacific Consensus Recommendations on X‐Linked Hypophosphatemia: Diagnosis, Multidisciplinary Management, and Transition From Pediatric to Adult Care

Asia‐Pacific Consensus Recommendations on X‐Linked Hypophosphatemia: Diagnosis, Multidisciplinary Management, and Transition From Pediatric to Adult Care

Latin-American consensus on the transition into adult life of patients with X-linked hypophosphatemia

The International X-Linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data

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