Almenabawy Nihal, Bahl Shalini, Ostlund Alyssa-Lyn, Ghai-Jain Shailly, Sosova Iveta, Chan Alicia, Mercimek-Andrews Saadet
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Princess Margaret Cancer Centre, 101 College Street, Toronto, ON M5G 1L7, Canada.
Mol Genet Metab Rep. 2024 Jan 25;38:101055. doi: 10.1016/j.ymgmr.2024.101055. eCollection 2024 Mar.
Galactosemia type I is an autosomal recessive disorder of galactose metabolism due to galactose-1-phosphate uridyltransferase deficiency, encoded by . To investigate the phenotypes, genotypes and long-term outcomes of galactosemia, we performed a retrospective cohort study in our center.
All individuals with galactosemia type I were included. We divided individuals into two groups to compare the outcomes of those treated symptomatically (SymX) and asymptomatically (AsymX). We reviewed electronic patient charts for clinical features, biochemical investigations, molecular genetic investigations, treatments, and outcomes.
There were 25 individuals including classic ( = 17), clinical variant ( = 4), and biochemical variant (Duarte) galactosemia ( = 4). Twelve individuals were diagnosed symptomatically (SymX), and 9 individuals were diagnosed asymptomatically (AsymX). We did not include individuals with biochemical variant (Duarte) galactosemia into any of these groups. At the time of the diagnosis, conjugated hyperbilirubinemia was present in 83.3% of SymX group, whereas only 22% of AsymX group. SymX group had hepatomegaly (25%), failure to thrive (33.3%), cataract (16.7%) and sepsis (25%), whereas none of the individuals in the AsymX group had these clinical features. Fourteen variants in were identified including pathogenic/likely pathogenic ( = 12), and likely benign/benign ( = 2) variants. The vast majority of individuals with classic and clinical variant galactosemia were treated with a galactose-lactose-free diet for life ( = 20/21). Intellectual disability was present in 54.5% of the SymX group, and in 37.5% of the AsymX group as a long-term outcome. Tremors were present 50% of the SymX group, and in 22% of the AsymX group as a long-term outcome. Although, intellectual disability and tremors seem to be less common in the AsymX group, there was no statistically significant difference between both groups. Primary ovarian insufficiency was present 50% of the SymX group, whereas in 20% of the AsymX group in post-pubertal females. We report a novel hypomorphic variant (p.Ala303Ser) in one individual with clinical variant galactosemia. We also report an individual with clinical variant galactosemia with normal urine galactitol levels on a normal diet.
It seems that newborn screening and early administration of a galactose-lactose-free diet decreases the long-term galactosemia-associated complications but does not prevent them completely. It may be that not all individuals with clinical variant galactosemia may need a galactose-lactose-free diet. It is timely to find new therapeutic strategies that can reduce the frequency of late-onset complications in galactosemia.
I型半乳糖血症是一种常染色体隐性遗传的半乳糖代谢紊乱疾病，由1-磷酸半乳糖尿苷转移酶缺乏引起，该酶由[相关基因]编码。为了研究半乳糖血症的表型、基因型及长期预后，我们在本中心开展了一项回顾性队列研究。
纳入所有I型半乳糖血症患者。我们将患者分为两组，比较有症状治疗组（SymX）和无症状组（AsymX）的预后情况。我们查阅电子病历，了解临床特征、生化检查、分子遗传学检查、治疗方法及预后情况。
共有25例患者，包括典型（n = 17）、临床变异型（n = 4）和生化变异型（杜氏型）半乳糖血症（n = 4）。12例患者有症状时被诊断（SymX），9例患者无症状时被诊断（AsymX）。我们未将生化变异型（杜氏型）半乳糖血症患者纳入上述任何一组。诊断时，SymX组83.3%出现结合胆红素血症，而AsymX组仅为22%。SymX组有肝肿大（25%）、生长发育迟缓（33.3%）、白内障（16.7%）和败血症（25%），而AsymX组患者均无这些临床特征。在[相关基因]中鉴定出14种变异，包括致病/可能致病（n = 12）和可能良性/良性（n = 2）变异。绝大多数典型和临床变异型半乳糖血症患者终身接受无半乳糖-乳糖饮食治疗（n = 20/21）。作为长期预后，SymX组54.5%出现智力残疾，AsymX组为37.5%。SymX组50%出现震颤，AsymX组为22%。虽然AsymX组智力残疾和震颤似乎较少见，但两组间无统计学显著差异。青春期后女性中，SymX组50%出现原发性卵巢功能不全，而AsymX组为20%。我们报告了1例临床变异型半乳糖血症患者的一种新的低表达变异（p.Ala303Ser）。我们还报告了1例临床变异型半乳糖血症患者在正常饮食下尿半乳糖醇水平正常。
新生儿筛查及早期给予无半乳糖-乳糖饮食似乎可减少半乳糖血症相关的长期并发症，但不能完全预防。可能并非所有临床变异型半乳糖血症患者都需要无半乳糖-乳糖饮食。及时寻找新的治疗策略以降低半乳糖血症迟发性并发症的发生率很有必要。
