Lysosomal acid lipase deficiency manifestations in children and adults: Baseline data from an international registry

Abstract

AbstractBackground and AimsLysosomal 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.MethodsIn 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.ResultsOf 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.ConclusionsAlthough 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.Trial registration numberNCT01633489.