Doctors' Perceptions of Rare Bone Disorders and X-Linked Hypophosphatemia: A Survey from Africa and the Middle East

Abstract

Objectives To assess the perceptions of genetic and metabolic bone disorders with a focus on X-linked hypophosphatemia (XLH) in the Middle East and Africa.

Materials and Methods An online survey of a convenience sample of physicians from relevant disciplines. The questions covered respondents' profiles, awareness of rare bone diseases, and XLH's burden, symptoms, and management.

Results A total of 139 respondents were included in the analysis. Responses came from the Arabian Gulf (41.7%), Middle East (20.1%), North Africa (17.3%), and Sub-Saharan Africa (20.9%). The largest single specialty was endocrinology (41%). When asked, 16 (11.5%) could not know about any metabolic/genetic bone diseases, and 123 respondents (88.5%) stated that they could think/were aware of some metabolic/genetic bone diseases, 111 enumerated various genetic and metabolic disorders. When they were presented with a typical case scenario of XLH, 18.0% of the respondents admitted ignorance of any possibility. However, 82.0% indicated having some idea of the condition. Of the latter group, 109 provided suggestions for possible diagnosis; the top single diagnosis was XLH. A smaller proportion of adult physicians had patients with symptoms attributed to XLH. Around three-quarters of respondents were aware of conventional therapy for XLH with vitamin D and phosphate supplementation. However, 89.8% of respondents welcomed specific biological therapy.

Conclusions Physicians are reasonably aware of XLH but have variable knowledge. They are unsatisfied with its conventional treatment. More in-depth knowledge of recognizing and modern management of bone metabolic and genetic conditions should be enhanced, particularly among adult physicians.

Keywords

hypophosphatemia - rickets - X-linked hypophosphatemia (XLH) - genetic bone diseases - metabolic bone diseases - rare bone diseases - Burosumab

Introduction

Rare endocrine-metabolic diseases represent an important area in medicine and pharmacology. The rare diseases of particular interest to endocrinologists involve all fields of endocrinology with the possible involvement of multiple endocrine glands.[1] Bone and mineral diseases encompass various conditions that involve altered skeletal homeostasis and are frequently associated with changes in circulating calcium, phosphate, or vitamin D metabolites.[2] They are commonly associated with severe clinical consequences and have a genetic etiology.[3] [4] Diagnosing these disorders requires a detailed clinical assessment of the wide variety of symptoms and signs associated with these diseases. Thus, clinicians should be aware of the relevant features of a careful history and physical examination, followed by appropriate laboratory and skeletal imaging investigations.[5] Finally, clinicians should be familiar with the range of molecular genetic tests available to ensure appropriate use and interpretation.[4] [5]

Although genetic and metabolic bone diseases present more often during early childhood,[1] [2] [3] they may also be seen in similar or different forms in adolescence and adulthood.[6] [7] The rare nature of these conditions may lead to late recognition, low diagnostic rates, and inadequate or inappropriate management. Recent advances enabled more diagnostic and management opportunities for many of these conditions. For example, X-linked hypophosphatemia (XLH) is the commonest form of inherited hypophosphatemia, caused by a mutation in the PHEX gene, leading to excessive expression of the phosphaturic factor FGF23. Symptoms are chiefly related to rickets in children and osteomalacia in adults causing several complications that can be highly invalidating.[8] Perhaps due to its rarity, XLH is poorly known, and diagnosis may frequently be delayed despite the availability of comprehensive national, regional, and international guidelines.[9] [10] [11] Conventional treatment has been based on oral phosphate salt supplementation and activated vitamin D analogs which cannot cure the disease. Over the past decade, several advanced treatment options have been introduced and shown to be effective for many metabolic bone disorders, such as Burosumab for XLH.[12] On the other hand, other disorders remain under-recognized in many world regions. Therefore, familiarity with these rare endocrine diseases remains a crucial factor in the early recognition and diagnosis of physicians who are likely to contact such patients during childhood, adolescence, and adulthood.

Surveying physicians' perceptions, attitudes, and practices is a commonly used approach or proxy method for assessing disease burden and care provision and exploring the role of innovative work behavior in health care with particular relevance to rare disorders.[13] [14] [15] Several surveys on the management pattern of common endocrine conditions in the Middle East and Africa (MEA) region have been recently conducted.[16] [17] [18] In the present study, we wished to scope the awareness and perception of physicians in the MEA region concerning certain genetic and metabolic bone diseases in general and XLH as an example of a condition with both conventional and specific therapy. The principal aim was to provide baseline information/data to direct future education.

Materials and Methods

This survey aimed to assess the level of awareness of physicians from two developing regions concerning certain genetic and metabolic bone diseases in general and XLH in particular. The survey included diagnosis, conventional management, and recent advances. A cross-sectional electronic survey was conducted between July and December 2019.

A focused literature search on the study area was undertaken to work with a writing group for a related article.[11] Another survey conducted in Europe with similar objectives was also reviewed. A questionnaire based on the search inspired by the above survey was adopted and finalized after attending an in-depth workshop on XLH at a rare disease center in Paris.[19] The questionnaire was converted into an online version by a commercial software provider. Some additional questions are deemed necessary for the target regions of interest. Due to the dual objectives of the survey, the questions were organized from general to more focused and specific areas to avoid giving hints. The questionnaire consisted of multiple-choice questions, including free-text answers for some open questions. The [Supplementary Material] ([Supplementary Appendix 1] [available in the online version]) provides the survey questions and predetermined responses. After obtaining informed consent, the survey then presented the participants with 20 questions arranged in 5 domains: (I) demographic and professional profile (8); (II) awareness of rare genetic/metabolic bone disease (2); (III) awareness of XLH (2); (IV) Symptoms of XLH (3); and (V) management of XLH (5).

A web-based commercial survey management service (Survey Monkey, Palo Alto, California, United States) was used. All participants received an initial email that explained the rationale of the survey and what was required from the consented respondents, followed by three subsequent reminder emails during the study period. Each message included an explanation of the rationale and method of participation, full credentials, and contact details of the principal investigator, together with a unique email-specific electronic link to the questionnaire. The survey service automatically blocked repeated submissions from the same IP address. The voluntary nature of the contribution, the unconditional right to decline participation and opt-out from the database, and the confidentiality of participant details were all confirmed. Data were collected anonymously, and the questionnaire text was available in English and French, the two languages used by medical professionals in the target regions. The survey Web site was open for the 6-month study period from July 1, 2019 to December 31, 2019. In the end, survey responses were collected and stored electronically for an anonymous analysis.

In the absence of a single MEA regional endocrine society with a membership list that can define a study population, the target population was identified from a list of electronic mails pooled from continuous professional development delegates, speakers, authors, or members of various scientific groups or forums in various parts of the MEA region. Consequently, several questions were added to the survey to help define the demographic and professional profiles of the respondents and their practices, similar to our previously published studies.[16] [17] [18]

Summary statistics were prepared for responses to each question. Because not every participant answered all questions, the percentage of respondents providing a given answer was calculated individually for each question, using the number of respondents to that question in the denominator.

Results

Respondents' Demographic and Professional Profiles

A total of 262 responses were received, of which 139 were deemed analyzable. Nonrespondents, those who declined consent, and those with substantially inadequate answers were excluded from the analysis. The largest proportion, 58 (41.7%), practiced in the Arabian Gulf, 28 (20.1%) in the rest of the Middle East, 24 (17.3%) in North Africa, and 29 (20.9%) respondents were from Sub-Saharan Africa. The demographic and professional profiles of the participants are detailed in [Table 1]. The largest specialty represented was endocrinology, with 41% of respondents (adult 35.3%, pediatric 5.7%), followed by 23 general physicians or pediatricians with an interest in endocrinology (16.5%) and 14 (10.1%) primary care physicians ([Table 1]). Of the group as a whole, 53 (38.1%) treat adults only, 55 (39.6%) treat children only, and 31 (22.3%) manage both age groups. Among the respondents, 33 (23.7%) have been in clinical practice for 10 years, whereas 27.3 and 28.1% have been in clinical practice for 11 to 20 and 21 to 30 years, respectively. The majority of respondents (71.2%) were senior physicians. Over two-thirds of respondents (68.5%) practice in tertiary level centers, and 15.8% practice in district or community hospitals/polyclinics. The proportion of time spent in direct patient care, as opposed to research, teaching, and administration, was 75 to 53.2% ([Table 1]).

Table 1 Demographics and professional profiles of the respondents

Questions and potential responses	Results
Please indicate the age group you manage:
Adults only	53 (38.1%)
Children only	55 (39.6%)
Both	31 (22.3%)
How best you describe your specialty:
Endocrinologists (adult and pediatric)	57 (41.1%)
Medicine/pediatrics with endocrine interest	23 (16.5%)
Primary care physicians	14 (10.1%)
All other specialties not listed	13 (9.4%)
General pediatrics	11 (7.9%)
General internist	10 (7.2%)
Nephrologists (adult or pediatric)	4 (2.9%)
Rheumatologists and orthopaedic surgeons	4 (2.8%)
Neurologists (adult or pediatric)	3 (2.2%)
Number of years have been in practice since graduation:
<10 years	22 (23.7%)
11–20 years	38 (27.3%)
21–30 years	39 (28.1%)
31–40 years	20 (14.4%)
>40 years	9 (6.5%)
Current professional career stage:
Senior (consultant/attending)	99 (71.2%)
Mid-grade (specialist/fellow)	40 (28.8%)
Nature of clinical practice setting:
University or teaching hospital/specialized center (tertiary)	95 (68.3%)
District or community (nonteaching) hospital/polyclinic	22 (15.8%)
Primary care/family medicine	16 (11.5%)
Other services (police, army, employer-based)	6 (4.3%)

Awareness of Rare Genetic/Metabolic Bone Disease and XLH

The detailed responses to the two questions included in this section are shown in [Table 2]. When asked, “thinking of metabolic/genetic bone diseases, which specific diseases, if any, come to mind? 16 (11.5%) responded that they do not know about any metabolic/genetic bone diseases, and 123 respondents (88.5%) stated that they could think of some metabolic/genetic bone diseases and of these 111 respondents enumerated various genetic and metabolic disorders. The top five responses in decreasing frequency were: osteogenesis imperfecta (44), osteoporosis (31), rickets (23), osteomalacia (22), and achondroplasia (11).

Table 2 Awareness of rare genetic/metabolic bone disease and XLH in physicians whose patients are adults and those whose patients are mostly in the pediatric age group

Questions and potential responses	Responses by age group of treated patients
	Adults	Pediatric
When thinking of metabolic/genetic bone diseases, which specific diseases, if any, come to your mind:
I do not know of any:	7 (13.2%)	4 (7.3%)
I can think of some:	46 (86.8%)	51 (92.7%)
Please take a moment to read the disease description and list of symptoms detailed in [Fig. 1]. What disease do you think this description refers to?
I do not know:	14 (26.4%)	4 (7.3%)
I have some idea about the condition	39 (73.6%)	9 (2.7%)
Have you heard of a metabolic bone disease called XLH?
Yes	41 (83.7%)	55 (100%)
No	8 (16.3%)	0 (0%)
How did you hear about it for the first time?
From own readings.	26 (53.1%)	14 (25.5%)
I looked after a patient or suspected patient.	9 (18.4%)	9 (16.4%)
It was mentioned in a discussion about a patient.	7 (14.3%)	27 (49.1%)
It was mentioned in a lecture/presentation.	1 (2.0%)	1 (1.8%)
I have attended a meeting on XLH or rare bone disorders.	1 (2.0%)	3 (5.5%)
I received an email alert about it.	2 (4.1%)	0 (0%)
It was mentioned to me by a medical representative.	3 (6.1%)	1 (1.8%)
If there were a biological treatment available specifically for XLH, would you be more likely to refer patients for treatment?
Yes	40 (85.1%)	51 (94.4%)
No	7 (14.9%)	3 (5.6%)

Abbreviation: XLH, X-linked hypophosphatemia.

Awareness of Respondents of the Symptoms and Management of XLH

In the second question, respondents were given a typical case scenario suggestive of XLH ([Fig. 1]). The responses are detailed in [Table 3]. Twenty-five respondents (18.0%) indicated not knowing what disease this description refers to, whereas 114 (82.0%) stated they had some idea about the condition. Of the latter group, 109 provided suggestions for a possible diagnosis. When respondents were asked if they had heard of a metabolic bone disease called XLH, 120 of 135 (88.9%) confirmed that they had heard about it before, and 15 (11.1%) had not heard of XLH before. Of those who confirmed some prior knowledge of XLH, 45.0% were aware of it through independent reading, and 30.8% had come across the disease in the context of patient care or managing a patient suspected of having a bone mineral disease or XLH; 15.8% stated that they had seen it mentioned in a lecture/presentation, 3.3% stated they had attended a special meeting on XLH or rare bone disorders (3.3%), and the remaining respondents stated they had heard of it from a colleague in a discussion about a patient or mentioned by a medical representative. Pediatric physicians tended to have a more in-depth awareness of practical-based knowledge than adult physicians. To evaluate the perceived frequency of encountered symptoms compatible with XLH and how they manage them, three questions were asked. First, the respondents were asked if they had seen patients without a firm diagnosis and a few symptoms, listed below, in the previous 12 months. The responses included short stature (by 65.9%), lower limb deformity (by 56.6%), bone or joint pain (by 53.5%), weakness/fatigue (51.2%), fractures (41.9%), active dental problems (33.3%), and previous corrective osteotomies or joint replacements (21.7%). Next, the respondents were asked how many patients without a firm diagnosis could be consistent with the following symptoms (short stature, lower limb deformity, bone or joint pain, weakness/fatigue, fractures, active dental problems, previous corrective osteotomies, or joint replacements) have they seen in the last 12 months? The responses (129) were no patients (31.8%), 1 to 3 patients (48.8%), 4 to 6 patients (9.3%), 7 to 12 patients (3.9%), and more than 12 patients (6.5%). Furthermore, respondents were asked how many patients that you selected in the previous question (i.e., without a firm diagnosis that you have seen in the previous 12 months, based on the following symptoms: short stature, lower limb deformity, bone or joint pain, weakness/fatigue, fractures, active dental problems, previous corrective osteotomies, or joint replacements) could have XLH? Nearly half of the respondents, 61/129 (47.3%), thought none. Other responses included one patient (22.5%), two patients (14.7%), three patients (5.4%), four patients (2.3%), more than five (4.7%), and others (3.1%).

Fig. 1 The index case of typical case scenario suggestive of XLH provided to form the basis of the survey section on XLH.

Table 3 Awareness of respondents of the symptoms and management of XLH

Questions and potential responses	Responses by age group of treated patients
	Adults	Pediatric
Have you seen patients without a firm diagnosis who would be presented with a couple or a few of the symptoms below in the last 12 months? (Check all that apply):
Short stature	23 (48.9%)	46 (83.6%)
Lower limb deformity	19 (40.4%)	41 (74.5%)
Bone or joint pain	31 (66.0%)	25 (45.5%)
Weakness/fatigue	27 (57.4%)	24 (43.6%)
Fractures	19 (40.4%)	22 (40.0%)
Active dental problems	9 (19.1%)	25 (45.5%)
Previous corrective osteotomies or joint replacements	8 (17.0%)	16 (29.1%)
How many patients without a firm diagnosis, who would be consistent with the symptoms listed above have you seen in the last 12 months?
None	21 (44.7%)	9 (16.4%)
1–6	13 (48.9%)	38 (68.1%)
>6	3 (6.4%)	8 (14.6%)
Are there any patients in your care who are currently being investigated or screened for XLH?
Yes	5 (10.6%)	29 (53.7%)
No	42 (89.4%)	25 (46.3%)
From practical experience or general knowledge, which of the following did you (or would you) use to treat XLH?
Phosphate supplements	31 (66.0%)	43 (79.6%)
Vitamin D preparations (either alfacalcidol or calcitriol)	31 (66.0%)	47 (87.0%)
Pain medications: (opiates or nonopiates)	13 (27.7%)	17 (31.5%)
Biologics	3 (6.4%)	1 (1.9%)
Burosumab	9 (19.1%)	17 (31.5%)
No treatment is usually needed	1 (2.1%)	0 (0%)
No treatment available	0 (0%)	0 (0%)
Other	0 (0%)	2 (3.7%)
If there were a biological treatment available specifically for XLH, would you be more likely to refer patients for treatment?
Yes	40 (85.1%)	51 (94.4%)
No	7 (14.9%)	3 (5.6%)

Abbreviation: XLH, X-linked hypophosphatemia.

First, respondents were asked if they had any patients being investigated or screened for XLH at the time of the survey. Most of the respondents (90/128, 70.3%) had no patients, and only 38 respondents (29.7%) confirmed having patients in this category. Second, from their practical experience or general knowledge, they were asked to name which treatments to use in patients with a potential diagnosis of XLH. In a decreasing order of frequency, the top three responses included: active vitamin D analogs such as alfacalcidol or calcitriol (75.8%), phosphate supplements (71.1%), and pain control medications including opiates or nonopiates (32.0%). Burosumab was identified by 25.8% of respondents. Other therapies were chosen by a minority, including biologics (5.5%); the remaining respondents stated that neither treatment is available, needed (3.2%), nor provided (4.7%). When respondents were also asked if they would be more likely to refer patients for treatment if a biologic therapy was available specifically for XLH, 89.8% confirmed they would refer patients to others. There was a trend for pediatric physicians to undertake more roles in management and treatments, whereas adult physicians tended to undertake diagnosis and referrals ([Table 4]).

Table 4 Respondents' views on the organization of care for patients suspected or confirmed to have XLH

Questions and potential responses	Responses by age group of treated patients
	Adults	Pediatric
What would be your primary role in managing patients who have symptoms consistent with XLH?
Diagnosis	26 (55.3%)	38 (70.4%)
Treatment	15 (31.9%)	27 (50.0%)
Management	19 (40.4%)	38 (70.4%)
Referral	26 (55.3%)	20 (37.0%)
Other	1 (2.1%)	0 (0%)
To whom would you refer XLH patients for treatment with the biologic described in the above question?
Family medicine physician	2 (4.3%)	2 (3.8%)
Pain specialist	3 (6.4%)	5 (9.4%)
Endocrinologist	37 (78.7%)	38 (71.7%)
Nephrologist	4 (8.5%)	17 (32.1%)
Rheumatologist	19 (40.4%)	5 (9.4%)
Orthopaedic surgeon	7 (14.9%)	16 (30.2%)
Other	3 (6.4%)	2 (3.8%)

Abbreviation: XLH, X-linked hypophosphatemia.

Perceived Professional Roles in Delivery and Organization of Care

The perceived roles in the delivery and organization of care of patients with symptoms consistent with XLH are shown separately for adult and pediatric physicians in [Table 4]. Out of 128 respondents, 62.5% considered their role mainly in diagnosis, 53.1% stated they felt their primary role was in general management, 46.9% in making a referral, and 40.6% would be involved in actual treatment (40.6%). Furthermore, respondents indicated that they would refer to the following four specialties (either pediatric or adult) of any XLH patient for treatment with biologic therapy if available: in a decreasing frequency, endocrinology, rheumatology, orthopaedic surgery, and nephrology, but less likely to refer to a pain clinic or other specialties. Physicians dealing with the pediatric age group favor more referrals to nephrologists and orthopaedic surgeons ([Table 4]).

Discussion

The current report provides a survey of physicians practicing in the MEA region regarding their general awareness of the burden and clinical management of genetic and metabolic bone disorders and their awareness, knowledge, and management of XLH. In particular, we have used an analogous survey instrument previously employed in an international survey tested as a market research tool in Europe (personal communication).

Most respondents were qualified endocrinologists or physicians interested in endocrinology in many countries, providing a comprehensive view of the region, albeit not homogeneously. Our respondents treat both adult and pediatric age groups. At least one-third had been in practice for 10 years, and over one-half have been practicing between 11 and 30 years. Therefore, our participants are likely to represent physicians who may look after suspected and confirmed cases of XLH.

Due to the low prevalence of XLH, awareness and knowledge of the physicians are paramount to drive screening, identification, and referral to management and may need innovative work behavior.[14] For instance, the experts' opinion survey conducted across Italian centers collected data on XLH epidemiology, diagnosis, and treatment using a questionnaire reflecting 175 patients' data over 20 years.[15] The diagnosis was made chiefly during childhood. The authors underscored that XLH remains a severe condition with significant morbidity, multiple presentations, and variable treatment approaches.[15] The situation may be particularly relevant in the MEA region, where the medical profession may not be structured similarly to developed countries.

A recent study included pediatric endocrinologists exclusively and may not reflect the broader image.[20] In the present study, although 88.9% of participants had heard about XLH, their awareness of the symptoms was limited. This may result in a lack of credibility as patients may hesitate to take further advice from nonexpert health care professionals with no in-depth knowledge about XLH. A recent detailed interprofessional mixed-methods study on adults living with XLH revealed that they are experiencing, among other concerns, chronic pain and fear of falling.[21] There are no data of this nature from the MEA region. We would, however, expect similar problems from the local patient population, particularly if faced with health care providers with no experience in XLH management. Therefore, it is imperative to raise health care providers' awareness about the impact of such conditions on patients' well-being. To this end, the present study and that of Deeb et al are valuable needs-assessment exercises for identifying gaps in the knowledge to help in planning education and training activities.[20] The two studies targeted slightly different populations with some overlap and used instruments with different emphases. Thus, their results should be viewed as complementary.

Only a third of the responders had encountered a patient living with XLH or suspected of the disease. This may be attributed to the low rates of identification and confirmation of the diagnosis, particularly a noticeable number of the respondents who practice in tertiary hospitals and are in the most relevant specialty, endocrinology. Alternatively, it may be an utter reflection of the condition's rarity in general. Notwithstanding, the higher rates of consanguinity furniture for increased rates of inherited genetic conditions have been well documented in many parts of the region. For instance, data from Qatar suggest a significant role of parental consanguinity in increasing the prevalence of genetic disorders, mainly autosomal recessive disorders.[22] Also, this issue was elaborated further with many lessons learned from a large-scale, first-tier clinical exome sequencing in a highly consanguineous population in Saudi Arabia.[23] These observations argue for the practice and research relevance of the present study. Although the prevalence of disease in MEA is not known precisely, there is a fair volume of information in several case reports and presentations in conferences and workshops.[24] [25] [26] [27] [28] [29]

Only a quarter of the respondents were aware of Burosumab, approved by the American and European regulatory bodies in 2018.[30] Burosumab is now a standard approach in all guidelines and expert opinions.[9] [10] [11] [12] A minority of respondents in the present study had patients with XLH in their clinics. Nonetheless, it is reassuring that most of them included suspected hypophosphatemic rickets as the likely diagnosis in the survey's case scenario, although many considered osteogenesis imperfecta at the top of their differential diagnosis. Many of them are aware of XLH, and around 70 to 75% were aware of the mainstay of conventional therapy. Although this was an indirect question, most respondents perceive conventional therapy as inadequate for XLH as 89.8% confirmed that they would refer for more specific treatment if it existed. This concurs with the findings of Deeb et al, who posed this question more directly.[20] Previous studies of physicians and patients addressed the reasons behind the perceived inadequacy of conventional treatment.[15] [21] These included poor compliance related to multiple doses, gastrointestinal side effects and unfavored palatability, reduced final height persistence of skeletal deformities, and appearance of nephrocalcinosis as a complication. In the other regional survey, the most familiar suggested reasons for the inadequacy of conventional treatment were reduced final height, inability to revert skeletal deformities, poor compliance, and associated nephrocalcinosis.[20] We have not included such details in more depth in our survey, as our target population was much more comprehensive, and it was felt inappropriate.

The present study has some limitations worthy of note. First, it is limited by its nature of a survey of reported perceptions and recalled patterns of practice rather than an actual quality assurance using preset key performance indicators. Second, the number of responders is relatively tiny. Third, the sample is not homogeneously representative of the targeted region. Nonetheless, the survey provides a baseline bird's eye view of the level of awareness and recognition, including mixed participants from pediatric and adult physicians, of XLH in the MEA region. It underscores some gaps in the knowledge of this genetic condition. The information can be used to develop focused, continuous professional development programs for physicians likely to be involved in XLH care.

Conclusion

Physicians in the MEA region are reasonably aware of XLH but have variable perceptions and expected practices. They are largely unsatisfied with its conventional treatment, and the majority are prepared to refer patients for more specific treatment if available. Endocrinologists view the care of XLH as appropriate for their specialty and seem keen to keep its management within the endocrine practice. Raising awareness of the recognition and modern management of XLH is needed. The formation of rare bone diseases or XLH interest groups within existing regional bodies, unconditionally supported by the pharmaceutical and scientific industry, would define the epidemiology, enhance knowledge, and maintain a seamless contact with international forums and centers of excellence that should translate to better patient care in the region.

Conflict of Interest

None declared.

Acknowledgment

The authors would like to express gratitude to all respondents who participated in the survey.

Authors' Contribution

All named authors contributed to the conception and conduct of the study. They have all contributed substantially to the drafting and revision of the manuscript and approved its final version.

Compliance with Ethical Principles

The study was approved by the Institutional Review Board of SKMC, Abu Dhabi and all participants provided informed electronic consent before getting access to the survey questionnaire. Responses were analyzed anonymously.

• References

• 1 Marcucci G, Cianferotti L, Beck-Peccoz P. et al. Rare diseases in clinical endocrinology: a taxonomic classification system. J Endocrinol Invest 2015; 38 (02) 193-259
• 2 Masi L, Agnusdei D, Bilezikian J. et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int 2015; 26 (10) 2529-2558
• 3 Charoenngam N, Cevik MB, Holick MF. Diagnosis and management of pediatric metabolic bone diseases associated with skeletal fragility. Curr Opin Pediatr 2020; 32 (04) 560-573
• 4 Hannan FM, Newey PJ, Whyte MP, Thakker RV. Genetics of skeletal disorders. Handb Exp Pharmacol 2020; 262: 325-351
• 5 Hannan FM, Newey PJ, Whyte MP, Thakker RV. Genetic approaches to metabolic bone diseases. Br J Clin Pharmacol 2019; 85 (06) 1147-1160
• 6 Linglart A, Biosse-Duplan M, Briot K. et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect 2014; 3 (01) R13-R30
• 7 Chesher D, Oddy M, Darbar U. et al. Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J Inherit Metab Dis 2018; 41 (05) 865-876
• 8 Beck-Nielsen SS, Mughal Z, Haffner D. et al. FGF23 and its role in X-linked hypophosphatemia-related morbidity. Orphanet J Rare Dis 2019; 14 (01) 58
• 9 Haffner D, Emma F, Eastwood DM. et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol 2019; 15 (07) 435-455
• 10 Bacchetta J, Rothenbuhler A, Gueorguieva I. et al. X-linked hypophosphatemia and burosumab: Practical clinical points from the French experience. Joint Bone Spine 2021; 88 (05) 105208
• 11 Al Juraibah F, Al Amiri E, Al Dubayee M. et al. Diagnosis and management of X-linked hypophosphatemia in children and adolescent in the Gulf Cooperation Council countries. Arch Osteoporos 2021; 16 (01) 52
• 12 Lambert AS, Zhukouskaya V, Rothenbuhler A, Linglart A. X-linked hypophosphatemia: Management and treatment prospects. Joint Bone Spine 2019; 86 (06) 731-738
• 13 Santesso N, Akl E, Bhandari M. et al. A practical guide for using a survey about attitudes and behaviors to inform health care decisions. J Clin Epidemiol 2020; 128: 93-100
• 14 Kessel M, Hannemann-Weber H, Kratzer J. Innovative work behavior in healthcare: the benefit of operational guidelines in the treatment of rare diseases. Health Policy 2012; 105 (2–3): 146-153
• 15 Emma F, Cappa M, Antoniazzi F. et al. X-linked hypophosphatemic rickets: an Italian experts' opinion survey. Ital J Pediatr 2019; 45 (01) 67
• 16 Beshyah SA, Sherif IH, Mustafa HE, Saadi HF. Patterns of clinical management of hypothyroidism in adults: an electronic survey of physicians from the Middle East and Africa. J Diabetes Endocr Pract 2021; 4: 75-82
• 17 Beshyah SA, Ali KF. Management of adrenal insufficiency: a survey of perceptions and practices of physicians from the Middle East and North Africa. J Diabetes Endocr Pract 2021; 4 (03) 125-130
• 18 Beshyah SA, Khalil AB. Clinical practice patterns in the management of thyroid nodules: first survey from the Middle East and Africa. J Diabetes Endocr Pract 2021; 4 (04) 167-174
• 19 Alsaffar H, Beshyah SA. Gulf X-linked hypophosphatemia preceptorship: July 4–6, 2019, Bicêtre Paris sud hospital, Paris, France. Ibnosina J Med Biomed Sci 2019; 11: 196-203
• 20 Deeb A, Juraibah FA, Dubayee MA, Habeb A. X-linked hypophosphatemic rickets: awareness, knowledge, and practice of pediatric endocrinologists in Arab countries. J Pediatr Genet 2020; 11 (02) 126-131
• 21 Hughes M, Macica C, Meriano C, Doyle M. Giving credence to the experience of X–linked hypophosphatemia in adulthood: an interprofessional mixed-methods study. J Patient Cent Res Rev 2020; 7 (02) 176-188
• 22 Ben-Omran T, Al Ghanim K, Yavarna T. et al. Effects of consanguinity in a cohort of subjects with certain genetic disorders in Qatar. Mol Genet Genomic Med 2020; 8 (01) e1051
• 23 Monies D, Abouelhoda M, Assoum M. et al. Lessons learned from large-scale, first-tier clinical exome sequencing in a highly consanguineous population. Am J Hum Genet 2019; 104 (06) 1182-1201
• 24 Al Dubayee M, Al Fattouh R, Al Juraibah F, Al Mutairi F, Babiker A. Novel homozygous mutation in CYP27B1 gene of vitamin D dependent rickets type 1A: a case report. Eur J Med Case Rep 2018; 2: 2-5
• 25 Al Jurayyan NA, Mohamed S, Al Issa SD, Al Jurayyan AN. Rickets and osteomalacia in Saudi children and adolescents attending endocrine clinic, Riyadh, Saudi Arabia. Sudan J Paediatr 2012; 12 (01) 56-63
• 26 Al-Atawi MS, Al-Alwan IA, Al-Mutair AN, Tamim HM, Al-Jurayyan NA. Epidemiology of nutritional rickets in children. Saudi J Kidney Dis Transpl 2009; 20 (02) 260-265
• 27 al-Gazali LI, Bener A, Abdulrazzaq YM, Micallef R, al-Khayat AI, Gaber T. Consanguineous marriages in the United Arab Emirates. J Biosoc Sci 1997; 29 (04) 491-497
• 28 Alsaffar H, Senniappan S, Linglart A. On X-linked hypophosphatemia at the European society of pediatric endocrinology meeting, Vienna, Austria; September 19–21, 2019. Ibnosina J Med Biomed Sci 2020; 12: 68-73
• 29 Deeb A, Habib A, Al Jasmi F, Mughal Z, Shaw N. Proceedings of the second Middle East Metabolic Bone Course; 10–11th March 2017, Dubai, UAE. J Rare Disord Diagn Ther 2018; 4 (S1): 8
• 30 Athonvarangkul D, Insogna KL. New therapies for hypophosphatemia-related to FGF23 excess. Calcif Tissue Int 2021; 108 (01) 143-157

Publication History

Article published online:
13 September 2022