Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Liver Int. 2023 Jul;43(7):1537-1547. doi: 10.1111/liv.15620. Epub 2023 May 24.
Lysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease involving lysosomal accumulation of cholesteryl esters and triglycerides. The International Lysosomal Acid Lipase Deficiency Registry (NCT01633489), established in 2013 to understand LAL-D natural history and long-term outcomes, is accessible to centres caring for patients diagnosed by deficient LAL activity and/or biallelic pathogenic LIPA variants. We describe the registry population enrolled through 2 May 2022.
In this prospective observational study, we analysed demographic and baseline clinical characteristics of children (ages ≥6 months to <18 years) and adults diagnosed with LAL-D.
Of 228 patients with confirmed disease, 61% were children; 202/220 (92%) with data on race were white. Median age was 5.5 years at sign/symptom onset and 10.5 years at diagnosis; median time from sign/symptom onset to diagnostic testing was 3.3 years. The most common manifestations raising suspicion of disease were elevated alanine (70%) and aspartate aminotransferase levels (67%) and hepatomegaly (63%). Among 157 with reported LIPA mutations, 70 were homozygous and 45 were compound heterozygous for the common exon 8 splice junction pathogenic variant (E8SJM-1). Seventy percent (159/228) of patients had dyslipidaemia. Among 118 with liver biopsies, 63% had microvesicular steatosis exclusively, 23% had mixed micro- and macrovesicular steatosis and 47% had lobular inflammation. Of 78 patients with fibrosis-stage data, 37% had bridging fibrosis and 14% had cirrhosis.
Although LAL-D signs/symptoms occur early, diagnosis is often delayed. Abnormal transaminase levels associated with hepatomegaly and dyslipidaemia should raise suspicion and prompt earlier diagnosis of LAL-D.
NCT01633489.
溶酶体酸性脂肪酶缺乏症（LAL-D）是一种罕见的常染色体隐性疾病，涉及溶酶体中胆固醇酯和三酰甘油的积累。国际溶酶体酸性脂肪酶缺乏症登记处（NCT01633489）成立于 2013 年，旨在了解 LAL-D 的自然病史和长期结局，可供诊断为缺乏 LAL 活性和/或双等位基因致病性 LIPA 变异的患者的中心使用。我们描述了截至 2022 年 5 月 2 日登记处的入组人群。
在这项前瞻性观察性研究中，我们分析了确诊为 LAL-D 的儿童（年龄≥6 个月至＜18 岁）和成人的人口统计学和基线临床特征。
在 228 例确诊为该病的患者中，61%为儿童；202/220 例（92%）有数据的患者为白人。起病时的中位年龄为 5.5 岁，确诊时的中位年龄为 10.5 岁；从起病到诊断性检查的中位时间为 3.3 年。最常见的表现为丙氨酸（70%）和天冬氨酸转氨酶水平升高（67%）和肝肿大（63%），提示疾病存在。在 157 例报告的 LIPA 突变中，70 例为纯合子，45 例为常见外显子 8 剪接接头致病性变异（E8SJM-1）的复合杂合子。70%（159/228）的患者存在血脂异常。在 118 例行肝活检的患者中，63%仅表现为微小泡性脂肪变性，23%为混合微小和大泡性脂肪变性，47%为肝小叶炎症。在 78 例有纤维化分期数据的患者中，37%有桥接纤维化，14%有肝硬化。
尽管 LAL-D 的症状/体征很早就出现，但诊断往往被延误。伴有肝肿大和血脂异常的异常转氨酶水平应引起怀疑，并促使对 LAL-D 的早期诊断。
NCT01633489。
