title: Growth in PHEX-associated X-linked hypophosphatemic rickets: the importance of early treatment.
abstract: Inactivating mutations in phosphate-regulating endopeptidase (PHEX) cause X-linked hypophosphatemic rickets (XLHR) characterized by phosphaturia, hypophosphatemia, bony deformities, and growth retardation. We assessed the efficacy of combined calcitriol and orally administered phosphate (Pi) therapy on longitudinal growth in relation to age at treatment onset in a retrospective, single-center review of children with XLHR and documented PHEX mutations. Growth was compared in those who started treatment before (G1; N = 10; six boys) and after (G2; N = 13; five boys) 1 year old. Median height standard deviation score (HSDS) at treatment onset was normal in G1: 0.1 [interquartile range (IR) -1.3 to 0.4) and significantly (p = 0.004) lower in G2 (IR -2.1 (-2.8 to -1.4). Treatment duration was similar [G1 8.5 (4.0-15.2) vs G2 11.9 (6.2-14.3) years; p = 0.56], as were prescribed phosphate and calcitriol doses. Recent HSDS was significantly (p = 0.009) better in G1 [-0.7 (-1.5 to 0.3)] vs G2 [-2.0 (-2.3 to -1.0)]. No effects of gender or genotype on growth could be identified. Children with PHEX-associated XLHR benefit from early treatment and can achieve normal growth. Minimal catchup growth was seen in those who started treatment later. Our findings emphasize the importance of early diagnosis to allow treatment before growth has been compromised.
authors.affiliation: Department of Nephro-Urology, Great Ormond Street Hospital, London, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Quinlan
authors.forename: Katie
authors.initials: K
authors.lastname: Guegan
authors.forename: Amaka
authors.initials: A
authors.lastname: Offiah
authors.forename: Richard O'
authors.initials: RO
authors.lastname: Neill
authors.forename: Melanie P
authors.initials: MP
authors.lastname: Hiorns
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.forename: William Van't
authors.initials: WV
authors.lastname: Hoff
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Waters
mesh_terms: D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002117:Calcitriol / Q000008:administration & dosage*; D053098:Familial Hypophosphatemic Rickets / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked; D048788:Growth and Development / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics; D010710:Phosphates / Q000008:administration & dosage*; D012189:Retrospective Studies
chemical_list: D050071:Bone Density Conservation Agents; D010710:Phosphates; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; D002117:Calcitriol
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