Early initiation of enzyme replacement therapy (ERT) with sebelipase alfa in patients with Wolman disease led to 100% survival with positive outcomes, according to the results of a nationwide cohort study with up to 10 years of follow-up.

Wolman disease is a rapidly progressing form of lysosomal acid lipase deficiency (LAL-D) which is characterized by the body’s inability to break down lipids due to a faulty enzyme. One of the most promising strategies to manage LAL-D is ERT that aims to restore the levels of functional LAL. 

Clinical trials testing the safety and efficacy of the ERT sebelipase alfa in patients with Wolman disease have shown that the approach improved survival, growth, and biological parameters. However, these trials followed patients for up to 5 years and the long-term effects of the treatment on health-related quality of life were thus far lacking.

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Here, a team of researchers led by Anaïs Brassier, MD, conducted a nationwide study of the effect of sebelipase alfa in patients with Wolman disease, as published in the Orphanet Journal of Rare Diseases.

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The researchers followed 5 patients with no LAL activity for a median of 7 years. Patients started treatment with ERT between ages 0 to 4 months. Their long-term tolerance to ERT was excellent with only 1 of them needing systematic premedication.

The patients were also treated with cholestyramine, fat-soluble vitamin supplements, and a specific diet high in medium-chain triglycerides and low in long-chain fatty acids. The results showed that these treatments led to improvements in liver function tests, plasma lipid profiles, levels of fat-soluble vitamins, and growth parameters. 

Three patients had footdrop, a waddling gait, or muscle fatigue but these were only transient. The results of the electromyography and muscle strength tests were normal. 

At the last follow-up, no patients had died. They all had normal growth parameters and none required special education. The health-related quality of life of all patients was satisfactory.

“Early diagnosis and treatment initiation [are] key features to reach good clinical outcomes,” the authors concluded. 


Demaret T, Lacaille F, Wicker C, et al. Sebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up. Orphanet J Rare Dis. 2021;16(1):507. doi:10.1186/s13023-021-02134-3