enzyme replacement therapy
lysosomal acid lipase deficiency
lysosomal storage disease
MetadataShow full item record
JournalDrug design, development and therapy
AbstractLysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dyslipidemia, as a consequence of cholesteryl esters and triglyceride accumulation, predominately in the liver and vascular and reticuloendothelial system. Significant morbidity can arise, due to liver failure and/or atherosclerosis; in part related to the severity of the underlying gene defect and corresponding enzyme deficiency. Diagnosis is based on demonstration of decreased LAL enzyme activity, complemented by analysis of the cognate gene defects. Therapeutic options include dietary manipulation and the use of lipid-lowering drugs. Sebelipase alfa, a recombinant enzyme replacement therapy, has garnered regulatory approval, following demonstration of improvements in disease-relevant markers and clinical benefit in clinical trials, which included increased survival in the most severe cases.
- Hepatic cholesteryl ester accumulation in lysosomal acid lipase deficiency: non-invasive identification and treatment monitoring by magnetic resonance.
- Authors: Thelwall PE, Smith FE, Leavitt MC, Canty D, Hu W, Hollingsworth KG, Thoma C, Trenell MI, Taylor R, Rutkowski JV, Blamire AM, Quinn AG
- Issue date: 2013 Sep
- Lysosomal acid lipase deficiency allograft recurrence and liver failure- clinical outcomes of 18 liver transplantation patients.
- Authors: Bernstein DL, Lobritto S, Iuga A, Remotti H, Schiano T, Fiel MI, Balwani M
- Issue date: 2018 May
- Lysosomal acid lipase deficiency: Expanding differential diagnosis.
- Authors: Valayannopoulos V, Mengel E, Brassier A, Grabowski G
- Issue date: 2017 Jan - Feb
- A Case of Lysosomal Acid Lipase Deficiency Confirmed by Response to Sebelipase Alfa Therapy.
- Authors: Shen JJ, Davis JL, Hong X, Laningham FH, Gelb MH, Kim GE
- Issue date: 2020 Dec
- Benefit of Treatment With Sebelipase-Alfa in a 63-Year-Old Patient With Advanced Liver and Atherosclerotic Disease Due to Lysosomal Acid Lipase Deficiency (LAL-D).
- Authors: Aigner E, Feldman A, Neureiter D, Datz C, Ratziu V, Paulweber B
- Issue date: 2018 Mar