Effect of GH replacement therapy in two male siblings with combined X-linked hypophosphatemia and partial GH deficiency.
OBJECTIVE
X-linked hypophosphatemia (XLH) is characterized by low serum phosphorus, relative 1,25-dihydroxyvitamin D(3) deficiency and rickets. It is caused by mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX). The conventional treatment of XLH includes the administration of phosphate and calcitriol; however, treated patients usually present with a short stature. Therefore, additional coexistent defects, such as GH deficiency, are under debate.


METHODS
Two male siblings presented with a disproportionate growth failure and rickets. Investigation of calcium and phosphate metabolism, molecular genetic analysis of the PHEX gene and GH function tests were initiated.


RESULTS
Both patients showed typical clinical and biochemical signs of XLH. Molecular genetic analysis revealed a 747 CGA (Arg)-TGA (End) mutation in exon 22 of the PHEX gene, confirming XLH. Since treatment with phosphate and calcitriol alone failed to improve growth in both patients, the GH axis was examined and a partial GH deficiency was diagnosed in both cases. Almost 3 Years of additional therapy with recombinant human GH (rhGH) led to a significant improvement of height standard deviation scores (HtSDS).


CONCLUSIONS
Poor growth in XLH may, in at least some patients, be aggravated by GH deficiency. Hence, GH deficiency should be considered in extremely poorly growing patients with XLH, because these patients are likely to benefit from rhGH therapy.
D001827:Body Height; D002117:Calcitriol / Q000627:therapeutic use; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D005091:Exons; D008040:Genetic Linkage; D006130:Growth Disorders / Q000188:drug therapy / Q000209:etiology; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010710:Phosphates / Q000627:therapeutic use; D011506:Proteins / Q000235:genetics
D018972:Insulin-Like Growth Factor Binding Protein 3; D010710:Phosphates; D011506:Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; D002117:Calcitriol