Garrett Olivia S, Druss Jared J, Vos E Naomi, Fu Yu-Ting Debbie, Lucia Stephanie, Greenstein Patricia E, Bauer Anna, Sykut-Cegielska Jolanta, Stepien Karolina M, Arbuckle Cameron, Grafakou Olga, Meyer Uta, Vanhoutvin Nele, Pané Adriana, Bosch Annet M, Rubio-Gozalbo Estela, Berry Gerard T, Fridovich-Keil Judith L
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
MosaKids Children's Hospital, Department of Pediatrics, Maastricht University Medical Center, Maastricht, Netherlands.
J Inherit Metab Dis. 2025 Jan;48(1):e12786. doi: 10.1002/jimd.12786. Epub 2024 Aug 14.
Long-term outcomes in classic galactosemia (CG) have been studied previously, but all prior studies have relied on cohorts of patients that were small in number, or heavily skewed toward children and young adults, or both. Here, we extend what is known about the health and well-being of maturing adults with CG by analyzing the results of anonymous custom surveys completed by 92 affected individuals, ages 30-78, and 38 unaffected sibling controls, ages 30-79. The median age for patients was 38.5 years and for controls was 41 years. These study participants hailed from 12 different countries predominantly representing Europe and North America. Participants reported on their general life experiences and outcomes in seven different domains including: speech/voice/language, cognition, motor function, cataracts, bone health, psychosocial well-being, and gastrointestinal health. We also queried women about ovarian function. Our results indicated a prevalence of long-term complications across all outcome domains that aligned with levels previously reported in younger cohorts. Given the sample size and age range of participants in this study, these findings strongly suggest that the adverse developmental outcomes commonly linked to CG are not progressive with age for most patients. We also tested four candidate modifiers for possible association with each of the outcomes followed, including: days of neonatal milk exposure, rigor of dietary galactose restriction in early childhood, current age, and home continent. We observed no associations that reached even nominal significance, except for the following: cataracts with neonatal milk exposure (p = 2.347e-04), cataracts with age (p = 0.018), and bone health with home continent (p = 0.03).
经典型半乳糖血症(CG)的长期预后此前已有研究,但所有既往研究均依赖数量较少的患者队列,或严重偏向儿童和青年,或两者皆有。在此,我们通过分析92名年龄在30 - 78岁的受影响个体以及38名年龄在30 - 79岁的未受影响的同胞对照完成的匿名定制调查问卷结果,扩展了对成年CG患者健康状况的认识。患者的中位年龄为38.5岁,对照的中位年龄为41岁。这些研究参与者来自12个不同国家,主要代表欧洲和北美。参与者报告了他们在七个不同领域的一般生活经历和预后情况,包括:言语/声音/语言、认知、运动功能、白内障、骨骼健康、心理社会幸福感和胃肠道健康。我们还询问了女性的卵巢功能。我们的结果表明,所有预后领域的长期并发症患病率与先前在较年轻队列中报告的水平一致。鉴于本研究中参与者的样本量和年龄范围,这些发现强烈表明,对于大多数患者而言,通常与CG相关的不良发育后果不会随着年龄增长而进展。我们还测试了四个候选修饰因素与后续每个预后结果的可能关联,包括:新生儿接触牛奶的天数、幼儿期饮食中半乳糖限制的严格程度、当前年龄和所在大陆。我们未观察到任何达到甚至名义显著性的关联,除了以下情况:白内障与新生儿接触牛奶(p = 2.347e - 04)、白内障与年龄(p = 0.018)以及骨骼健康与所在大陆(p = 0.03)。