Lysosomal acid lipase deficiency (LAL-D) is a rare disorder of
cholesterol metabolism with an autosomal recessive mode of inheritance. The absence or deficiency of the LAL
enzyme gives rise to pathological accumulation of
cholesterol esters in various tissues. A severe LAL-D phenotype manifesting in infancy is associated with adrenal calcification and liver and gastrointestinal involvement with characteristic early mortality. LAL-D presenting in childhood and adulthood is associated with
hepatomegaly,
liver fibrosis,
cirrhosis, and premature
atherosclerosis. There are currently no curative pharmacological treatments for this life-threatening condition. Supportive management with
lipid-modifying agents does not ameliorate
disease progression.
Hematopoietic stem cell transplantation as a curative measure in infantile disease has mixed success and is associated with inherent risks and complications.
Sebelipase alfa (
Kanuma) is a recombinant human LAL
protein and the first
enzyme replacement therapy for the treatment of LAL-D. Clinical trials have been undertaken in infants with rapidly progressive LAL-D and in children and adults with later-onset LAL-D. Initial data have shown significant survival benefits in the infant group and improvements in biochemical parameters in the latter.
Sebelipase alfa has received marketing authorization in the United States and Europe as long-term
therapy for all affected individuals. The availability of
enzyme replacement therapy for this rare and progressive disorder warrants greater recognition and awareness by physicians.