Shire, a member of the Takeda group of companies, Lexington, MA, USA.
Present address: Pfizer, 610 Main St, Cambridge, MA, 02139, USA.
Orphanet J Rare Dis. 2019 Apr 29;14(1):89. doi: 10.1186/s13023-019-1060-2.
Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A. Neurological involvement results in severe disability and premature death, but understanding of the natural history of the disease remains limited. In this study, 32 caregivers of patients with MLD in the USA (16 with late-infantile MLD; 16 with juvenile MLD) were interviewed about their experiences of the disease. Qualitative analysis of the interview transcripts was performed to gain insights into symptom onset, the diagnostic process and disease progression, with a focus on the differences between late-infantile and juvenile MLD.
The mean ages of patients at interview were 7.6 years and 20.7 years for individuals with late-infantile and juvenile MLD, respectively. Patients with late-infantile MLD had a mean age of 1.5 years at symptom onset and 2.6 years at diagnosis. The most common initial symptoms in this group related to problems with gross motor function (12/16 patients); 11 patients never learned to walk independently. For patients with juvenile MLD, the mean ages at symptom onset and diagnosis were 8.7 years and 11.6 years, respectively. Cognitive or social/behavioural problems were the most common first reported symptoms in this group (9/16 and 7/16 patients, respectively); these were generally followed by deterioration in motor function. The rate of functional decline was more rapid in patients with late-infantile MLD than those with juvenile MLD; the mean time from first symptom to first functional loss was 1 year versus 6.1 years, respectively. Nine patients with juvenile MLD and three with late-infantile MLD had undergone a haematopoietic stem cell transplant; outcomes following transplant were variable.
Our data highlight clear overall differences in symptom profiles and disease progression between late-infantile and juvenile MLD, but also indicate some degree of interindividual variability within each subtype. These findings are broadly consistent with previously published descriptions of MLD and enhance our knowledge of the natural history of the disease, which ultimately should help to improve patient care and aid assessments of the effectiveness of disease-related interventions in the future.
异染性脑白质营养不良（MLD）是一种罕见的常染色体隐性溶酶体贮积病，由芳基硫酸酯酶 A 活性缺乏引起。神经受累导致严重残疾和过早死亡，但对疾病的自然史仍知之甚少。在这项研究中，美国 32 名 MLD 患者的照顾者（16 名晚发性婴儿型 MLD；16 名少年型 MLD）接受了有关疾病经历的访谈。对访谈记录进行定性分析，以深入了解症状发作、诊断过程和疾病进展，重点关注晚发性婴儿型和少年型 MLD 之间的差异。
接受访谈的患者的平均年龄分别为晚发性婴儿型 MLD 患者的 7.6 岁和少年型 MLD 患者的 20.7 岁。晚发性婴儿型 MLD 患者的症状发作年龄平均为 1.5 岁，诊断年龄为 2.6 岁。该组中最常见的首发症状与粗大运动功能问题有关（16 例中有 12 例）；11 例患者从未独立行走。少年型 MLD 患者的症状发作和诊断年龄分别为 8.7 岁和 11.6 岁。认知或社会/行为问题是该组中最常见的首发症状（16 例中有 9 例和 7 例患者）；这些症状通常随后出现运动功能恶化。晚发性婴儿型 MLD 患者的功能下降速度比少年型 MLD 患者更快；首次出现症状至首次功能丧失的平均时间分别为 1 年和 6.1 年。9 名少年型 MLD 患者和 3 名晚发性婴儿型 MLD 患者接受了造血干细胞移植；移植后的结果各不相同。
我们的数据突出显示了晚发性婴儿型和少年型 MLD 之间症状谱和疾病进展的明显总体差异，但也表明每个亚型内存在一定程度的个体间变异性。这些发现与先前发表的 MLD 描述基本一致，并增强了我们对疾病自然史的认识，这最终应有助于改善患者护理，并有助于未来评估疾病相关干预措施的有效性。
