%0 Journal Article
%T Pubertal origin of growth retardation in inborn errors of protein metabolism: A longitudinal cohort study.
%A Busiah K
%A Roda C
%A Crosnier AS
%A Brassier A
%A Servais A
%A Wicker C
%A Dubois S
%A Assoun M
%A Belloche C
%A Ottolenghi C
%A Pontoizeau C
%A Souberbielle JC
%A Piketty ML
%A Perin L
%A Le Bouc Y
%A Arnoux JB
%A Netchine I
%A Imbard A
%A de Lonlay P
%J Mol Genet Metab
%V 141
%N 3
%D 2024 Mar 1
%M 38219674
%F 4.204
%R 10.1016/j.ymgme.2023.108123
%X <B>OBJECTIVE: </B>Inherited amino-acid metabolism disorders (IAAMDs) require lifelong protein-restricted diet. We aimed to investigate: 1/ whether IAAMDs was associated with growth, pubertal, bone mineral apparent density (BMAD) or body composition impairments; 2/ associations linking height, amino-acid mixture (AAM), plasma amino-acids and IGF1 concentrations.<BR><B>METHODS: </B>Retrospective longitudinal study of 213 patients with neonatal-onset urea cycle disorders (UCD,n = 77), organic aciduria (OA,n = 89), maple syrup urine disease (MSUD,n = 34), or tyrosinaemia type 1 (n = 13).<BR><B>METHODS: </B>We collected growth parameters, pubertal status, BMAD, body composition, protein-intake, and IGF1 throughout growth.<BR><B>RESULTS: </B>Overall final height (n = 69) was below target height (TH): -0.9(1.4) vs. -0.1(0.9) SD, p < 0.001. Final height was ≤ TH-2SD in 12 (21%) patients. Height ≤ - 2SD was more frequent during puberty than during early-infancy and pre-puberty: 23.5% vs. 6.9%, p = 0.002; and vs. 10.7%, p < 0.001. Pubertal delay was frequent (26.7%). Height (SD) was positively associated with isoleucine concentration: β, 0.008; 95%CI, 0.003 to 0.012; p = 0.001. In the pubertal subgroup, height (SD) was lower in patients with vs. without AAM supplementation: -1.22 (1.40) vs. -0.63 (1.46) (p = 0.02). In OA, height and median (IQR) isoleucine and valine concentrations(μmol/L) during puberty were lower in patients with vs. without AAM supplementation: -1.75 (1.30) vs. -0.33 (1.55) SD, p < 0.001; and 40 (23) vs. 60 (25) (p = 0.02) and 138 (92) vs. 191 (63) (p = 0.01), respectively. No correlation was found with IGF1. Lean-mass index was lower than fat-mass index: -2.03 (1.15) vs. -0.44 (0.89), p < 0.001.<BR><B>CONCLUSIONS: </B>In IAAMDs, growth retardation worsened during puberty which was delayed in all disease subgroups. Height seems linked to the disease, AAM composition and lower isoleucine concentration, independently of the GH-IGF1 pathway. We recommend close monitoring of diet during puberty.