Enzyme replacement therapy corrects Lysosomal Acid Lipase Deficiency (LALD) in a mouse model of Wolman disease/cholesteryl ester storage disease

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

“…Hyperalimentation via intravenous drip has been found to be only mildly effective [33]. Patients with WD do not live beyond the first year of life [34]. …”

“…Mutations in the LIPA gene are located in human chromosome 10q23.2-q23.3 and are autosomal recessive [34]. The LIPA gene contains 10 exons, 9 introns and is 36kb long.…”

“…To date, over a dozen different mutations in the LIPA gene have been reported for WD. The mutations are diverse and are usually nonsense mutations with deletions or insertions in the LIPA gene that ultimately result in the absence of a functional enzyme [34-53]. For example, a G to A substitution at nucleotide 347 in exon 4 converts a tryptophan codon into a termination codon in WD patients.…”

“…For example, a G to A substitution at nucleotide 347 in exon 4 converts a tryptophan codon into a termination codon in WD patients. CESD is generally caused by missense mutations in the LIPA gene, and are heteroallelic or homoallelic with other mutations in this gene, generating moderately functioning LAL from either or both alleles [34, 54]. A mutation common in CESD is the G -> A mutation at position -1 of the exon 8 splice donor site (c.894G>A; E8SJM) and accounts for an estimated 60% of all CESD cases.…”

“…The literature contains reports on only the most severe of these cases; thus, an underreporting of milder forms of the disease may skew our perception of its typical symptoms [34]. This underreporting also affects how we perceive CESD’s lethality, which is often due to liver failure [74].…”