학술논문
Pubertal origin of growth retardation in inborn errors of protein metabolism: A longitudinal cohort study.
Document Type
Academic Journal
Author
Busiah K; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France; Paediatric endocrinology, diabetology and obesity unit, Women-Mothers-Children Department, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. Electronic address: kanetee.busiah@chuv.ch.; Roda C; Université Paris Cité, HERA Team, CRESS, INSERM, INRAE, F-75004 Paris, France.; Crosnier AS; Endocrine function testing department, Assistance Publique-Hôpitaux de Paris, Trousseau University Hospital, Paris, France.; Brassier A; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France.; Servais A; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France.; Wicker C; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France; Pediatric Inherited Metabolic Diseases department, University Hospital of Strasbourg- Hautepierre, Strasbourg, France.; Dubois S; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France.; Assoun M; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France.; Belloche C; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France.; Ottolenghi C; Metabolic biochemistry, Necker Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Imagine Institute, Filière G2M, MetabERN, Medical School, Université Paris Cité, Paris, France.; Pontoizeau C; Metabolic biochemistry, Necker Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Imagine Institute, Filière G2M, MetabERN, Medical School, Université Paris Cité, Paris, France.; Souberbielle JC; Hormonology laboratory, Physiology department, Necker-Enfants Malades Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Piketty ML; Hormonology laboratory, Physiology department, Necker-Enfants Malades Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Perin L; Endocrine function testing department, Assistance Publique-Hôpitaux de Paris, Trousseau University Hospital, Paris, France.; Le Bouc Y; Endocrine function testing department, Assistance Publique-Hôpitaux de Paris, Trousseau University Hospital, Paris, France; Sorbonne University, INSERM, Saint Antoine research centre, Assistance Publique-Hôpitaux de Paris, Paris, France.; Arnoux JB; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France.; Netchine I; Endocrine function testing department, Assistance Publique-Hôpitaux de Paris, Trousseau University Hospital, Paris, France; Sorbonne University, INSERM, Saint Antoine research centre, Assistance Publique-Hôpitaux de Paris, Paris, France.; Imbard A; Metabolic biochemistry, Necker Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Imagine Institute, Filière G2M, MetabERN, Medical School, Université Paris Cité, Paris, France.; de Lonlay P; Inherited Metabolic Diseases Reference Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Filière G2M, MetabERN, Université Paris Cité, Paris, France; INSERM U1151, Necker-Enfants Malades Institute (INEM), Paris, France.
Source
Publisher: Academic Press Country of Publication: United States NLM ID: 9805456 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-7206 (Electronic) Linking ISSN: 10967192 NLM ISO Abbreviation: Mol Genet Metab Subsets: MEDLINE
Subject
Language
English
Abstract
Objectives: 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.
Design: 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).
Methods: We collected growth parameters, pubertal status, BMAD, body composition, protein-intake, and IGF1 throughout growth.
Results: 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.
Conclusions: 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.
Competing Interests: Declaration of competing interest None.
(Copyright © 2023. Published by Elsevier Inc.)
Design: 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).
Methods: We collected growth parameters, pubertal status, BMAD, body composition, protein-intake, and IGF1 throughout growth.
Results: 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.
Conclusions: 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.
Competing Interests: Declaration of competing interest None.
(Copyright © 2023. Published by Elsevier Inc.)