Background and Aims: 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. Methods: 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. Results: 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. Conclusions: 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. Trial registration number: NCT01633489.

Balwani, M., Balistreri, W., D'Antiga, L., Evans, J., Ros, E., Abel, F., et al. (2023). Lysosomal acid lipase deficiency manifestations in children and adults: Baseline data from an international registry. LIVER INTERNATIONAL, 43(7), 1537-1547 [10.1111/liv.15620].

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

D'Antiga L.;
2023

Abstract

Background and Aims: 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. Methods: 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. Results: 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. Conclusions: 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. Trial registration number: NCT01633489.
Articolo in rivista - Articolo scientifico
diagnosis; enzyme replacement therapy; fatty liver; hypercholesterolaemia; lysosomal storage diseases;
English
24-mag-2023
2023
43
7
1537
1547
none
Balwani, M., Balistreri, W., D'Antiga, L., Evans, J., Ros, E., Abel, F., et al. (2023). Lysosomal acid lipase deficiency manifestations in children and adults: Baseline data from an international registry. LIVER INTERNATIONAL, 43(7), 1537-1547 [10.1111/liv.15620].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/473785
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