X-linked hypophosphatemic rickets: A study (with literature review) of linear growth response to calcitriol and phosphate therapy

Abstract

Not all children with X-linked hypophosphatemia (XLH) have demonstrated improved linear growth with calcitriol [1,25-(OH)2D3] and inorganic phosphate (Pi) therapy. To assess which factors are associated with a favorable growth response during this treatment, we retrospectively compared demographics and biochemical parameters of bone metabolism to the linear growth patterns of 20 children with XLH who were prepubertal and had not required osteotomy. A total of 15 patients had family histories consistent with XLH; 5 appeared to be sporadic cases. During 3 years of therapy, the growth velocities of 12 patients had been at or above the mean for age (good growers) and those of 8 patients had been below the mean (poor growers). Data from the two groups were contrasted. We found no difference between the good growers and poor growers before or after the 3 year period of therapy in mean age, dietary calcium, calcitriol dose or compliance, or Pi dose or compliance. Both groups increased their mean fasting serum Pi levels with treatment. The TmP/GFR (mean +/- SEM) of the good growers improved with therapy (1.9 +/- 0.2 to 2.6 +/- 0.2 mg/dl, p = 0.01), and their posttreatment value was higher compared to that of the poor growers (2.6 +/- 0.1 versus 2.2 +/- 0.1 mg/dl, p = 0.02). However, their enhanced TmP/GFR was not associated with a reduction in serum iPTH levels (before, 693 +/- 50; after, 688 +/- 76 pg/ml; p = 0.9). The Z test for binomial proportions showed that the group that grew well contained a disproportionate number of girls (10 of 12, p = 0.04). Our findings suggest that calcitriol may exert a direct effect on the renal tubule to improve Pi reclamation in XLH. The observation that heterozygous girls appear to respond better than hemizygous boys to calcitriol and Pi therapy provides evidence for a gene dosage effect in the expression of this X-linked dominant disorder.

Results of deformity correction in children with X-linked hereditary hypophosphatemic rickets by external fixation or combined technique

“…The preoperative average serum phosphate level of 2.2 mg/ dL in our series is comparable with 2.0 mg/dL reported by Song et al [19] or 2.1 in a series by Petje et al [14]. Anyway, developed deformities of lower limbs should be surgically corrected in order to maintain normal biomechanical conditions for ambulating, for cosmetic reasons and to prevent severe early arthrosis of hip and knee joints [11,18,20,33].…”

“…Clinical orthopaedic features become obvious at the beginning of ambulating and are manifested by varus or valgus deformities of the lower limb, torsion deformities, impaired gait, short stature, and pathologic fractures [2,[7][8][9]. Traditional medical treatment is administration of phosphate substitution combined with vitamins [10][11][12]. Although, the conservative treatment is not always successful.…”

Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets

“…Inclusion criteria were the clinical diagnosis of XLH (i.e. family history, symptoms, physical evaluation consistent with XLH) and the presence of hypophosphatemia due to selective phosphate wasting in the absence of kidney malformations [20][21][22]. Patients not fulfilling the criteria for diagnosis of XLH [e.g.…”

Metabolic and orthopedic management of X-linked vitamin D-resistant hypophosphatemic rickets

“…1a-c). Medication treatment consists of oral phosphate substitution and supplementation of active vitamin D compounds [2][3][4][5][6]. Despite correct substitution the main symptoms, i.e., deformity, pain, small stature, and-in some cases-also fractures can occur.…”