Clinical Outcomes Solutions, Unit 68 Basepoint, Shearway Business Park, Shearway Road, Folkestone, Kent, CT19 4RH, UK.
Clinical Outcomes Solutions, Chicago, IL, USA.
Orphanet J Rare Dis. 2022 Mar 28;17(1):138. doi: 10.1186/s13023-022-02287-9.
Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Newborn screening and timely galactose-restricted diet can resolve acute symptoms and decrease fatalities. However, despite this, significant chronic, progressive morbidities remain which have a real impact upon daily life. To better understand the burden of disease, 20 in-depth qualitative interviews were undertaken with adult patients (n = 12), and their caregivers (n = 8), enrolled in the ACTION-Galactosemia trial, part of a clinical program designed to investigate the safety and efficacy of AT-007 (govorestat) in reducing toxic galactitol and long-term clinical outcomes in Classic Galactosemia.
Interviews revealed the substantial burden of Classic Galactosemia on patients and families. Most adults were not able to live independently, and all required support with day-to-day activities. Short- and long-term memory difficulties and tremors were identified as the most frequently experienced and challenging symptoms. Other difficulties such as fine motor skills and slow/slurred speech contribute to the significant impact on daily activities, affecting ability to communicate and interact with others. Symptoms were first noticed in early childhood and worsened with age. Classic Galactosemia impacted all areas of daily functioning and quality of life, leading to social isolation, anxiety, anger/frustration and depression. This demonstrates the significant burden of disease and challenges associated with Classic Galactosemia.
The impact on both patients and caregivers underscores the severity of the unmet medical need and the importance of pharmacological intervention to halt or prevent disease progression. Any treatment that could reduce symptoms or slow functional decline would ease the burden of this condition on patients and caregivers.
经典型半乳糖血症是一种罕见的常染色体隐性疾病，由于半乳糖-1-磷酸尿苷酰转移酶（GALT）严重缺乏/缺失，半乳糖不能正常代谢，转化为异常和有毒的代谢物半乳糖醇。新生儿筛查和及时的半乳糖限制饮食可以缓解急性症状并降低死亡率。然而，尽管如此，仍存在显著的慢性、进行性的病态，对日常生活有真正的影响。为了更好地了解疾病负担，我们对参加 ACTION-Galactosemia 试验的 20 名成年患者（n=12）及其照顾者（n=8）进行了 20 次深入的定性访谈，该试验是一项旨在研究 AT-007（govorestat）在降低经典型半乳糖血症中有毒半乳糖醇和长期临床结局的安全性和疗效的临床项目的一部分。
访谈揭示了经典型半乳糖血症对患者及其家庭的巨大负担。大多数成年人无法独立生活，所有人都需要日常活动的支持。短期和长期记忆困难以及震颤被确定为最常经历和最具挑战性的症状。其他困难，如精细运动技能和语速缓慢/口齿不清，也会对日常生活活动产生重大影响，影响与他人沟通和互动的能力。这些症状在儿童早期就开始出现，并随着年龄的增长而恶化。经典型半乳糖血症影响了日常生活的各个方面，降低了生活质量，导致社交孤立、焦虑、愤怒/沮丧和抑郁。这表明了疾病的严重负担以及与经典型半乳糖血症相关的挑战。
对患者和照顾者的影响强调了未满足的医疗需求的严重程度以及药物干预以阻止或预防疾病进展的重要性。任何能够减轻症状或减缓功能下降的治疗方法都将减轻这种疾病对患者和照顾者的负担。
