SAT-LB051 Longitudinal Growth in Height and Changes in Body Proportions in Children with Hereditary Hypophosphatemic Rickets in a Single Center

Abstract

Children with Hereditary Hyphophosphatemic Rickets (HHR) are characterized by hypophosphatemia, rickets and disproportionate short stature. Aim: To analyze growth pattern in height (H) and body proportions during childhood and puberty in a cohort of 96 children, 29 males (M), 67 females (F), with HHR treated with standard dosis of phosphorus and calcitriol followed in a single center. Methods: Body proportions were evaluated by sitting height/height (SH/H) ratio. Patients were divided in 2 groups (G) according to their compliance to treatment: good (G1) and poor (G2). Pubertal growth was evaluated by Preece Baines model 1in 19 patients (8 M, 11 F), while adult H was achieved in 42 patients (13 M, 29 F). Molecular characterization of PHEX gene was performed by automated sequencing analysis in 27 cases (8 familiar, 15 sporadic). Results: Birth weights and lengths were no different from national reference data in both sexes. At first appointment, median (range) age (years): 3.5 (0.2/14.6); H SDS: -2.3 (0.6/-5.88) and SH/H ratio SDS: 3.4 (-1.7/10.4). Mean growth velocity SDS (+/-SD) at take off was significantly higher in G1: -0.7 (0.6) than in G2: -2.6 (0.8) (p<0.00001). During puberty, mean growth velocity SDS (+/-SD) at peak was significantly higher in G1: -0.48 (1.38) than in G2: -2.73 (1.3) (p<0.002). Median (range) adult H SDS was significantly higher in M G1: -2.1 (-2.9/-1.8) and F G1: -2.4 (-3/-0.9) than in M G2: -4.7 (-6.9/-0.7) and F G2: -4.1 (-6.6/-2.7) (p<0.005). A tendency to higher mean total growth gain during puberty (cm) in G1 vs G2 in both sexes was found (p=0.1). Median (range) adult SH/H ratio SDS was significantly lower in G1: 2.32 (0.5/5.3) than in G2: 6.21 (2.5/8.1) (p=0.0016). PHEX gene deleterious variants were found in 87% of familiar and in 53% of sporadic cases and 6 novel mutations (p.Lys468Asn, c.2070+5G>A, Ex2 deletion, p.Gln666Ter, p.Gln682IlefsTer36, p.Met98SerfsTer10) were pathogenic by in silico tools. Conclusions: Patients with HHR were born with adequate length for gestational age. Short stature and body disproportion was already found at diagnosis. During childhood and puberty, growth retardation and body disproportions were maintained in G1 while were aggravated in G2. Consequently, adult H and body proportions were significantly better in G1. Early and appropriate diagnosis and treatment improve adult H and body proportions prognosis. Frequency of PHEX mutations was similar to other cohorts reported. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.