Lower Limb Deformity and Gait Deviations Among Adolescents and Adults With X-Linked Hypophosphatemia

Mindler, Gabriel T.; Kranzl, Andreas; Stauffer, Alexandra; Kocijan, Roland; Rudolf, G.; Radler, C; Haeusler, Gabriele; Raimann, Adalbert

doi:10.3389/fendo.2021.754084

Cited by 25 publications

(37 citation statements)

References 33 publications

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“…Characteristically, XLH is associated with multi-apical lower limb deformities in different planes. Frontal plane deformities such as valgus or varus malalignment, often accompanied by sagittal diaphyseal bowing (procurvatum) have been described in this disorder recently ( 4 , 5 ). Less information is available on disorder-specific sagittal plane deformities, typically procurvatum deformity of the femur, tibia, and fibula and on transverse plane deformities of the lower limb [maltorsion of femur and tibia/fibula ( 21 )].…”

Section: Discussionmentioning

confidence: 99%

“…Less information is available on disorder-specific sagittal plane deformities, typically procurvatum deformity of the femur, tibia, and fibula and on transverse plane deformities of the lower limb [maltorsion of femur and tibia/fibula ( 21 )]. Although the need for lower limb deformity analysis in the evaluation of XLH patients was mentioned in several studies ( 4 , 5 , 9 ), detailed quantitative radiographic data on the influence of pharmacological treatment on lower limb development is lacking. Linglart et al.…”

Section: Discussionmentioning

confidence: 99%

“…Torsional MRI is a reliable method to analyze femoral and tibial maltorsion ( 16 ) and is widely used in centers for lower limb deformity correction. Tibial malrotation in XLH has been reported ( 1 ) but only recently quantified using gait analysis ( 4 , 5 ). To the author’s knowledge, MRI data on femoral maltorsion in children with XLH has not been reported so far.…”

Section: Discussionmentioning

confidence: 99%

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Persistent Lower Limb Deformities Despite Amelioration of Rickets in X-Linked Hypophosphatemia (XLH) - A Prospective Observational Study

et al. 2022

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BackgroundGait deviations, lower limb pain and joint stiffness represent key symptoms in patients with X-linked hypophosphatemia (XLH, OMIM 307800), a rare disorder of mineral homeostasis. While the pathomechanism for rickets is well understood, the direct role of PHEX (Phosphate-regulating neutral endopeptidase) deficiency in non-rachitic features including complex deformities, skull and dental affections remains unclear. FGF23-inhibiting antibody treatment can normalize serum phosphate levels and to improve rickets in XLH patients. However, linear growth remains impaired and effects on lower limb deformity and gait are insufficiently studied.AimsTo characterize and evaluate the course of lower limb deformity in a case series of pediatric XLH patients receiving Burosumab therapy.MethodsComparative assessment of planar radiographs, gait analysis, biochemical and clinical features of pediatric patients before and ≥12 months after initiation of FGF23-inhibiting was performed prospectively. Lower limb maltorsion was quantified by torsional MRI and gait analysis. Standardized deformity analysis of lower limb anteroposterior radiographs was conducted.ResultsSeven patients (age 9.0 +/-3.6 years) were eligible for this study. All patients received conventional treatment before onset of antibody treatment. Maltorsion of the femur was observed in 8/14 legs using torsional MRI (mean antetorsion 8.79°). Maltorsion of the tibia was observed in 9/14 legs (mean external torsion 2.8°). Gait analysis confirmed MRI findings with femoral external malrotation prior to and one year after onset of Burosumab therapy. Internal foot progression (intoeing gait) remained pathological in all cases (mean 2.2°). Knee rotation was pathologically internal 10/14 legs. Mean mechanical axis deviation (MAD) of 16.1mm prior to Burosumab changed in average by 3.9mm. Three children underwent guided growth procedures within the observation period. Mild postprocedural rebound of frontal axis deviation was observed under Burosumab treatment in one patient.ConclusionsThis is the first study to investigate lower limb deformity parameters quantitatively in children with XLH receiving Burosumab. One year of Burosumab therapy was associated with persistent maltorsion and frontal axis deviation (varus/valgus) despite improved rickets in this small, prospective uncontrolled study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Persistent Lower Limb Deformities Despite Amelioration of Rickets in X-Linked Hypophosphatemia (XLH) - A Prospective Observational Study

et al. 2022

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“…High BMI has been reported in other studies of populations of patients with XLH. One third of children in an XLH population in France were reported to be overweight or obese [30], and adolescents and adults with XLH in Austria had a mean elevated BMI, with 35.0% reported as being overweight and 30.0% as obese [31]. However, data collected in this registry have shown that children and adults combine shorter stature with 'normal' weight, leading to an elevated BMI.…”

Section: Discussionmentioning

confidence: 76%

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

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Beck-Nielsen

Boot

et al. 2023

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Background: X-linked hypophosphataemia (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 this 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. Trial registration: Clinical Trials, NCT03193476. Registered 20 June 2017, https://clinicaltrials.gov/ct2/show/NCT03193476

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“…Nevertheless, XLH has lifelong clinical consequences such as short stature, musculoskeletal pain, complex skeletal deformities, disability among adults, premature osteoarthritis (OA) and enthesopathies ( 1 – 3 ). Lower limb deformities frequently occur in children and adolescents with XLH ( 4 , 5 ) possibly caused by changes in bone growth and/or surgical interventions ( 4 ). The skeletal deformities lead to impaired gait and decreased quality of life (QoL), which are associated with a high burden of disease in XLH patients ( 1 – 3 ).…”

Section: Introductionmentioning

confidence: 99%

The ankle in XLH: Reduced motion, power and quality of life

et al. 2023

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BackgroundX-linked hypophosphatemia (OMIM 307800) is a rare bone disease caused by a phosphate-wasting condition with lifelong clinical consequences. Those affected suffer from bone pain, complex skeletal deformities, impaired mobility and a reduced quality of life. Early osteoarthritis and reduced range of motion of the lower limbs are known pathologies in XLH patients. However, XLH-specific data on the affected compartments such as the ankle joint through the evaluation of radiographic and gait analysis data is still lacking.Patients and methodsIn this cross-sectional study, patients with genetically verified XLH, age ≥ 16 - 50 years and a complete record of gait analysis and or radiographic analysis data were included. Clinical examination, radiological and gait analysis data were compared to norms using the dataset of our gait laboratory registry. Radiographic analysis included tibial deformity analysis and assessment of osteoarthritis and enthesopathies. Western Ontario and McMaster Universities Arthritis Index (WOMAC), SF36v2, American Orthopedic Foot and Ankle Society score (AOFAS) and the Foot and Ankle Outcome Score (FAOS) were used. Twentythree participants with 46 limbs were eligible for the study.ResultsA total of 23 patients (n=46 feet) met the inclusion criteria. Patients with XLH had significantly reduced gait quality, ankle power and plantar flexion (p < 0.001) compared to a historic gait laboratory control group. Ankle valgus deformity was detected in 22 % and ankle varus deformity in 30 % of the patients. The subtalar joint (59.1%) as well as the anterior tibiotalar joint (31.1%) were the main localizations of moderate to severe joint space narrowing. Ankle power was decreased in moderate and severe subtalar joint space narrowing (p < 0.05) compared to normal subtalar joint space narrowing. No lateral or medial ligament instability of the ankle joint was found in clinical examination. Tibial procurvatum deformity led to lower ankle power (p < 0.05).ConclusionsThis study showed structural and functional changes of the ankle in patients with XLH. Subtalar ankle osteoarthritis, patient reported outcome scores and clinical ankle restriction resulted in lower gait quality and ankle power.

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Lower Limb Deformity and Gait Deviations Among Adolescents and Adults With X-Linked Hypophosphatemia

Cited by 25 publications

References 33 publications

Persistent Lower Limb Deformities Despite Amelioration of Rickets in X-Linked Hypophosphatemia (XLH) - A Prospective Observational Study

Persistent Lower Limb Deformities Despite Amelioration of Rickets in X-Linked Hypophosphatemia (XLH) - A Prospective Observational Study

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

The ankle in XLH: Reduced motion, power and quality of life

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