ESPE Abstracts (2019) 92 LB-11

Height in Inborn Errors of Metabolism Requiring Hypoprotidic Diet: A Longitudinal Follow Up Study About 213 Patients

kanetee Busiah1,2, Célina Roda3, Anaïs Brassier4, Clément Pontoizeau5,6, Chris Ottolenghi7,8, Marie Piketty9, Anne-Sophie Crosnier10, Laurence Perin10, Yves Le Bouc10, Irène Netchine10, Pascale De Lonlay2


1Pediatric Endocrinology, diabetology and obesity unit, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland. 2Reference center of Inherited Metabolic Diseases, Necker Enfants Malades University Hospital, APHP, Imagine institute, Filière G2M, metabERN, INEM, University Paris Descartes, Paris, France. 3Université Paris Descartes, Sorbonne Paris Cité, EA 4064, Epidémiologie environnementale, Paris, France. 4Reference center of Inherited Metabolic Diseases, Necker Enfants Malades University Hospital, APHP, Imagine institute, Filière G2M, metabERN, INEM, University Paris Descartes, paris, France. 5Reference center of Inherited Metabolic Diseases, Hospital Necker Enfants Malades, APHP, Imagine institute, Filière G2M, metabERN, INEM, University Paris Descartes, Paris, France. 6Metabolic biochemistry, Hospital Necker Enfants Malades, APHP, Imagine institute, Filière G2M, metabERN, University Paris Descartes,, Paris, France. 7Reference center of Inherited Metabolic Diseases, Hospital Necker Enfants Malades, APHP, Imagine institute, Filière G2M, metabERN, INEM, University Paris Descartes,, Paris, France. 8Metabolic biochemistry, Hospital Necker Enfants Malades, APHP, Imagine institute, Filière G2M, metabERN, University Paris Descartes,, Paris, France. 9Service des Explorations Fonctionnelles, Necker Enfants Malades Hospital, APHP, paris, France. 10Service des Explorations Fonctionnelles, Trousseau University Hospital, Paris, France


Background: Protein intake is crucial for growth. Many inherited metabolic diseases (IMD) require a strict controlled protein diet.

Aim: to evaluate growth, pubertal status and body composition in IMD requiring a strict controlled protein diet.

Patients & Méthods: Longitudinal follow up cohort study. We recorded data before 4years (early childhood, n=189); between 4 and 8years for girls and 9years for boys (prepuberty, n=168) and after 8/9years (puberty, n=136).

Results: 213 patients (mean age: 13.9years) were treated for urea cycle disorders (n=77), organic acidurias (n=89), maple syrup disease (n=34), tyrosinemia type I (n=13). 69 patients attained their final height that was lower than their target height (SDs): -0.90 (1.43) vs. -0.09 (0.85), P=0.0001. Mean height (SDs) was lower than target height in each subgroup of age (P<0.0001). In the pubertal subgroup, height was lower compared to early infancy and to prepubertal subgroups (-0.9 (1.5) vs. -0.3 (1.3) and vs. -0.3 (1.5) respectively, P<0.0001). Tanner stage was assessed in 91(81%) patients. Delayed puberty was frequent (24/91, 25.3%). In the pubertal subgroup, mean height was lower in patients receiving additional amino acid mixture free of pathological precursor (AAM) than in those who did not: -1.22 (0.18) vs. -0.63 (0.16), P=0.0182. In the subgroup receiving AAM, the natural protein intake expressed as percentage of recommended daily allowance, was lower than in the group that did not: 63.6 (22.1) vs. 90.4 (37.9), P=0.0023. Overall BMI Z-score was 0.4 (1.5) in early infancy, 0.5 (1.4) in prepubertal and pubertal subgroups. BMI Z-score was not different between patients with a height ≤-2DS and those with normal height. Body composition was performed in 55 patients aged 8 to 22.2 years. Mean Lean mass Index (LMI) z-score was -2.03 (1.15) and was significantly lower that Fat mass Index (FMI) (-0.44 [0.89], P<0.001). We found no difference in FMI or LMI between boys and girls.

Discussion: In this large cohort of IMD requiring a strict controlled protein diet, we found a growth retardation that progressively worsens from early childhood to puberty, leading to a final height lower than expected. Delayed puberty is frequent. Body composition in the pubertal subgroup showed a decreased LMI and a normal FMI despite normal BMI. One mechanism of growth retardation could be the lower amount of natural protein intake that is found in the pubertal subgroup. Further studies are required to confirm this hypothesis.