A Clinician's Guide to X-Linked Hypophosphatemia

Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.83). 07/2011; 26(7):1381-8. DOI: 10.1002/jbmr.340
Source: PubMed


X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines, which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the Advances in Rare Bone Diseases Scientific Conference held at the NIH in October 2008. We briefly review the clinical and pathophysiologic features of the disorder and offer this guide in response to the conference recommendation, based on our collective accumulated experience in the management of this complex disorder.

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    • "Metaphyseal changes of rickets are usually evident on radiographs. Osteomalacia (accumulation of unmineralized osteoid) is a characteristic of untreated HHR [6] "
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    ABSTRACT: Hereditary hypophosphatemic rickets (HHR) is a rare disorder of renal phosphate wasting and the most common form of heritable rickets. Here, we report a case of an active 25-year-old male with HHR showing atraumatic bilateral femoral neck pseudarthrosis after 4 years of consecutive knee pain. A conservative therapy was administered, taking into account both the risks of surgical treatment and the little impairment even in the sport activities which the patient experienced.
    Full-text · Article · May 2014
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    • "With the approval of the review board of our institute, we retrospectively reviewed the history of a total of 61 patients who were diagnosed with hypophosphatemic rickets between the years 2002 and 2008. Diagnosis was made by the presence of radiologic findings, such as long bone cupping, splaying, and fraying of the metaphyseal areas and lab values such as elevated alkaline phosphatase level, low 25-OH vitamin D, and low percent tubular reabsorption of phosphate (TRP) [6, 7]. Among the 61 patients who underwent corrective osteotomy and lengthening on both femur and tibial segment or either, only tibial segments were enrolled to minimize affecting variables and bias for this study. "
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    ABSTRACT: The aim of this study was to find out the ideal cut-off level of phosphate for safe healing when deformity correction and concomitant lengthening are indicated in the two different skeletal maturity groups of patients with rickets. Thirty-nine hypophosphatemic rickets patients were selected for the study and were divided into two groups: 27 skeletally immature (group IM) and 12 skeletally mature (group M). The outcomes were evaluated with respect to the healing index (HI), laboratory findings, and complications with the mean follow-up of 5.1 years (range, 3.1-7.9). The healing index (HI) of group IM was 1.44 month/cm and HI of group M was 1.68 month/cm. The negative correlation between the level of serum phosphate and HI in group M (coefficient = -0.94) was evaluated to be less than the correlation in group IM (coefficient = -0.50), indicating that the HI is more likely to be affected by serum phosphate in group M than in group IM. Preoperative serum phosphate levels of 2.3 mg/dL and 2.6 mg/dL were analyzed to be the cut-off values of group IM and group M, respectively, in which the cut-off points divided the series into two groups having the most significantly different HI.
    Full-text · Article · Apr 2014 · BioMed Research International
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    • "Careful supplementation of phosphorus and vitamin D in childhood is necessary to optimise growth and to prevent development of tertiary hyperparathyroidism and renal impairment [2]. Phosphorus therapy is associated with diarrhoea and is a stimulant to PTH secretion [13] as well as FGF23 secretion [14]; it is associated with nephrocalcinosis in treated patients with XLH [15] and thus normalisation of serum phosphorus is not the target of therapy in XLH [2]. Vitamin D supplementation is associated with hypercalciuria [15], hence monitoring of urinary as well as serum calcium is necessary to assess whether vitamin D dosage should be reduced. "
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    ABSTRACT: This is the first report of which the authors are aware to describe this c.2166delinsGG mutation in X-linked hypophosphataemia and to describe normalisation of renal threshold for phosphate excretion after parathyroidectomy for tertiary hyperparathyroidism in X-linked hypophosphataemia. We present the case of a 34-year-old Caucasian woman with X-linked hypophosphatemia. She developed tertiary hyperparathyroidism with markedly high bone turnover requiring total parathyroidectomy and had prolonged requirement for intravenous calcium infusion after surgery. She had a novel mutation in her phosphate-regulating gene with homologies to endopeptidases on the X-chromosome and had an unusual degree of dependence on phosphate supplementation. Prior to operative intervention she had a trial of cinacalcet that improved bone turnover markers when used in isolation but which led to a paradoxical rise in parathyroid hormone levels when given with phosphate supplementation. After correction of hungry bone syndrome, the renal phosphorus threshold normalised as a manifestation of hypoparathyroid state despite marked elevation in level of fibroblast growth factor 23. This case illustrates the risk of tertiary hyperparathyroidism as a complication of treatment for hypophosphataemia; it highlights the morbidity associated with hungry bone syndrome and provides novel insight into renal handling of phosphorus.
    Full-text · Article · Mar 2014 · Journal of Medical Case Reports
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