Abstract：
OBJECTIVE: 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.
METHODS: 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.
METHODS: 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.
摘要：
目的：遗传性氨基酸代谢紊乱（IAAMDs）需要终身限制蛋白质饮食。我们的目的是调查：1/IAAMD是否与生长有关，青春期,骨矿物质表观密度（BMAD）或身体成分受损；2/联系身高，氨基酸混合物（AAM），血浆氨基酸和IGF1浓度。
方法：回顾性纵向研究213例新生儿发作尿素循环障碍患者（UCD，n=77),有机酸尿症（OA，n=89),枫糖浆尿病（MSUD，n=34),或酪氨酸血症1型（n=13）。
方法：我们收集了生长参数，青春期状态,BMAD,身体成分,蛋白质摄入，和IGF1整个增长。
结果：最终身高（n=69）低于目标身高（TH）：-0.9（1.4）与-0.1(0.9)SD,p<0.001。12例（21%）患者最终身高≤TH-2SD。身高≤-2SD在青春期比在婴儿早期和青春期前更频繁：23.5％6.9%，p=0.002；和vs.10.7%,p<0.001。青春期延迟频繁(26.7%)。身高（SD）与异亮氨酸浓度呈正相关：β，0.008；95CI，0.003至0.012；p=0.001。在青春期亚组，患者的身高（SD）较低不补充AAM：-1.22（1.40）vs.-0.63（1.46）（p=0.02）。在OA,与青春期患者的身高和中位数（IQR）异亮氨酸和缬氨酸浓度（μmol/L）较低不补充AAM：-1.75（1.30）vs.-0.33（1.55）标准差，p<0.001；和40(23)vs.60（25）（p=0.02）和138（92）191(63)(p=0.01)，分别。与IGF1无相关性。瘦体重指数低于脂肪体重指数：-2.03（1.15）vs.-0.44（0.89），p<0.001。
结论：在IAAMD中，生长迟缓在青春期期间恶化，在所有疾病亚组中均延迟。身高似乎与疾病有关，AAM组成和较低的异亮氨酸浓度，独立于GH-IGF1途径。我们建议在青春期期间密切监测饮食。
方法：回顾性纵向研究213例新生儿发作尿素循环障碍患者（UCD，n=77),有机酸尿症（OA，n=89),枫糖浆尿病（MSUD，n=34),或酪氨酸血症1型（n=13）。
方法：我们收集了生长参数，青春期状态,BMAD,身体成分,蛋白质摄入，和IGF1整个增长。
结果：最终身高（n=69）低于目标身高（TH）：-0.9（1.4）与-0.1(0.9)SD,p<0.001。12例（21%）患者最终身高≤TH-2SD。身高≤-2SD在青春期比在婴儿早期和青春期前更频繁：23.5％6.9%，p=0.002；和vs.10.7%,p<0.001。青春期延迟频繁(26.7%)。身高（SD）与异亮氨酸浓度呈正相关：β，0.008；95CI，0.003至0.012；p=0.001。在青春期亚组，患者的身高（SD）较低不补充AAM：-1.22（1.40）vs.-0.63（1.46）（p=0.02）。在OA,与青春期患者的身高和中位数（IQR）异亮氨酸和缬氨酸浓度（μmol/L）较低不补充AAM：-1.75（1.30）vs.-0.33（1.55）标准差，p<0.001；和40(23)vs.60（25）（p=0.02）和138（92）191(63)(p=0.01)，分别。与IGF1无相关性。瘦体重指数低于脂肪体重指数：-2.03（1.15）vs.-0.44（0.89），p<0.001。
结论：在IAAMD中，生长迟缓在青春期期间恶化，在所有疾病亚组中均延迟。身高似乎与疾病有关，AAM组成和较低的异亮氨酸浓度，独立于GH-IGF1途径。我们建议在青春期期间密切监测饮食。
