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. 2019 May 7;3(7):1321-1334.
doi: 10.1210/js.2018-00365. eCollection 2019 Jul 1.

The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey

Alison Skrinar  1 , Melita Dvorak-Ewell  1 , Ayla Evins  1 , Carolyn Macica  2 , Agnès Linglart  3 , Erik A Imel  4 , Christina Theodore-Oklota  1 , Javier San Martin  1
Affiliations

The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey

Alison Skrinar et al. J Endocr Soc. .

Abstract

Context: X-linked hypophosphatemia (XLH) is characterized by excess fibroblast growth factor 23 (FGF23), hypophosphatemia, skeletal abnormalities, and growth impairment. We aimed to understand the burden of disease of XLH across the lifespan.

Methods: Responses were collected from adults with XLH and parents/caregivers of a child with XLH in an online survey, including multiple-choice and open-ended questions on demographics, disease manifestations, treatment history, assistive device use, and age-specific patient-reported outcomes (PROs).

Results: Data were collected from 232 adults with XLH (mean age, 45.6 years; 76% female) and 90 parents/caregivers of a child with XLH (mean age, 9.1 years; 56% female). Mean age recalled for symptom onset was 3.2 years for adults and 1.3 years for children. When surveyed, nearly all children (99%) and 64% of adults were receiving oral phosphate, active vitamin D, or both. Prior participation in a trial investigating burosumab, a fully human monoclonal antibody against FGF23, was reported in 3% of children and 10% of adults; of these respondents, only one child reported current treatment with burosumab at the time of the survey. Both children and adults reported typical features of XLH, including abnormal gait (84% and 86%, respectively), bowing of the tibia/fibula (72% and 77%), and short stature (80% and 86%). Nearly all adults (97%) and children (80%) reported bone or joint pain/stiffness. Adults reported a history of fractures (n/N = 102/232; 44%), with a mean (SD) age at first fracture of 26 (16) years. Adults reported osteophytes (46%), enthesopathy (27%), and spinal stenosis (19%). Mean scores for PROs evaluating pain, stiffness, and physical function were worse than population norms. Analgesics were taken at least once a week by 67% of adults.

Conclusions: Despite the common use of oral phosphate and active vitamin D established in the 1980s, children with XLH demonstrate a substantial disease burden, including pain and impaired physical functioning that persists, as demonstrated by similar responses reported in adults with XLH.

Keywords: X-linked hypophosphatemia; XLH; burden of disease; quality of life.

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Figures

Figure 1.
Figure 1.
Functioning and HRQoL in adults with XLH. (a) WOMAC results by domain; higher scores indicate worse pain, stiffness, and functioning. (b) BPI results by domain; mild scores range from 0 to 3, moderate scores range from 3 to 6, and severe scores range from 6 to 10. (c) SF-36v2 results by domain. Some SE values are too small to be visible on the graph (i.e., <1.0). MID, minimally important difference.
Figure 2.
Figure 2.
Functioning and HRQoL in children with XLH. (a) PODCI results by domain. (b) SF-10 results by summary score. MID, minimally important difference.
See this image and copyright information in PMC

References

    1. Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381–1388. - PMC - PubMed
    1. Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK. Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol. 2009;160(3):491–497. - PubMed
    1. Endo I, Fukumoto S, Ozono K, Namba N, Inoue D, Okazaki R, Yamauchi M, Sugimoto T, Minagawa M, Michigami T, Nagai M, Matsumoto T. Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: prevalence, biochemical data and treatment. Endocr J. 2015;62(9):811–816. - PubMed
    1. Rafaelsen SH, Johansson S, Raeder H, Bjerknes R. Hereditary hypophosphatemia in Norway; a retrospective population-based study of genotypes, phenotypes and treatment complications. Eur J Endocrinol. 2016;174(2):125–136. - PMC - PubMed
    1. Carpenter TO, Shaw NJ, Portale AA, Ward LM, Abrams SA, Pettifor JM. Rickets. Nat Rev Dis Primers. 2017;3:17101. - PubMed

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