Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Dec 13;16(24):4309.
doi: 10.3390/nu16244309.

Practical Recommendations for the Diagnosis and Management of Lysosomal Acid Lipase Deficiency with a Focus on Wolman Disease

Javier de Las Heras  1 , Carolina Almohalla  2 , Javier Blasco-Alonso  3 , Mafalda Bourbon  4   5 , Maria-Luz Couce  6 , María José de Castro López  7 , Mª Concepción García Jiménez  8 , David Gil Ortega  9 , Luisa González-Diéguez  10 , Silvia Meavilla  11 , Ana Moreno-Álvarez  12 , José Pastor-Rosado  13 , Paula Sánchez-Pintos  6 , Irene Serrano-Gonzalo  14   15 , Eduardo López  16 , Pedro Valdivielso  17 , Raquel Yahyaoui  18 , Jesús Quintero  19
Affiliations
Review

Practical Recommendations for the Diagnosis and Management of Lysosomal Acid Lipase Deficiency with a Focus on Wolman Disease

Javier de Las Heras et al. Nutrients. .

Abstract

Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease with two distinct phenotypes, an infantile-onset form (formerly Wolman disease) and a later-onset form (formerly cholesteryl ester storage disease). The objective of this narrative review is to examine the most important aspects of the diagnosis and treatment of LAL-D and to provide practical expert recommendations. The infantile-onset form occurs in the first weeks of life and is characterized by malnourishment and failure to thrive due to gastrointestinal impairment (vomiting, diarrhea, malabsorption), as well as systemic inflammation, hepatosplenomegaly, and adrenal calcifications. Mortality is close to 100% before one year of life in the absence of specific treatment. The later-onset form can be diagnosed in childhood or adulthood and is characterized by chronic liver injury and/or lipid profile alterations. When LAL-D is suspected, enzyme activity should be determined to confirm the diagnosis, with analysis from a dried blood spot sample being the quickest and most reliable method. In infantile-onset LAL-D, the initiation of enzyme replacement therapy (sebelipase α) and careful nutritional management with a low-lipid diet is very urgent, as prognosis is directly linked to the early initiation of specific treatment. In recent years, our knowledge of the management of LAL-D has increased considerably, with improvements regarding the initial enzyme replacement therapy dose and careful nutritional treatment with a low-lipid diet to decrease lipid deposition and systemic inflammation, leading to better outcomes. In this narrative review we offer a quick guide for the initial management of infantile-onset LAL-D.

Keywords: LAL-D; LIPA gene; Wolman disease; cholesteryl ester storage disease; diet; enzyme replacement therapy; infantile-onset lysosomal acid lipase deficiency; lysosomal acid lipase; lysosomal acid lipase deficiency; sebelipase.

PubMed Disclaimer

Conflict of interest statement

Javier de las Heras has received speaking and scientific consultancy fees from Astra Zeneca-Alexion. Carolina Almohalla received speaking fees from Astra Zeneca-Alexion. Javier Blasco-Alonso declares no conflicts of interest. Mafalda Bourbon received a project grant from SOBI. María-Luz Couce declares no conflicts of interest. María José de Castro López declares no conflicts of interest. Mª Concepción García Jiménez received speaking fees from Astra Zeneca-Alexion. David Gil Ortega received speaking fees from Astra Zeneca-Alexion. Luisa Gonzalez-Dieguez received speaking and scientific consultancy fees from Astra Zeneca-Alexion. Silvia Meavilla declares no conflicts of interest. Ana Moreno-Álvarez received speaking fees from Astra Zeneca-Alexion. José Pastor-Rosado has received conference payments from Astra Zeneca-Alexion; grants for attendance at scientific meetings, as well as fees for scientific consultancy from Astra Zeneca-Alexion Alexion. Paula Sánchez-Pintos received speaking fees from Astra Zeneca-Alexion. Irene Serrano-Gonzalo received speaking fees from Astra Zeneca-Alexion. Eduardo López is president of the Spanish LAL-D Patient Organization. That organization has received consultancy fees from Astra Zeneca-Alexion. Pedro Valdivielso has received honoraria for consulting, expert testimony, conferences, presentations, manuscripts or educational events from AstraZeneca-Alexion, Amgen, Sanofi, Novartis, Ferrer and Daiichi-Sankyo; meeting support from Amgen, Novartis, Ferrer, MSD, Daiichi-Sankyo, and Sanofi; and research grants/contracts from Ferrer, SOBI, Lipigon, Ionis, and Capenergy. Raquel Yahyaoui has received speaking fees and a research grant from Astra Zeneca-Alexion. Jesús Quintero has received honoraria for consulting, conferences, presentations, manuscripts or educational events from AstraZeneca-Alexion, IPSEN, Miru, and Orphalan; and research grants/contracts from IPSEN.

Figures

Figure 1
Figure 1
Abdominal X-ray showing adrenal gland calcifications in a patient with infantile-onset lysosomal acid lipase deficiency (LAL-D). Image courtesy of Dr. de las Heras.
Figure 2
Figure 2
Blood film examination showing lymphocytes with cytoplasmatic lipid vacuoles in a patient with infantile-onset lysosomal acid lipase deficiency (LAL-D). Image courtesy of Dr. de las Heras.
Figure 3
Figure 3
Algorithm for the diagnosis of infantile-onset lysosomal acid lipase deficiency (LAL-D). ASMD: acid sphingomyelinase deficiency; LAL: lysosomal acid lipase; LAL-D: lysosomal acid lipase deficiency; HDL: high-density lipoprotein; LDL: low-density lipoprotein; HLH: hemophagocytic lymphohistiocytosis.
Figure 4
Figure 4
Algorithm for the diagnosis of later-onset lysosomal acid lipase deficiency (LAL-D). ALT: alanine aminotransaminase; ASMD: acid sphingomyelinase deficiency; HBV: hepatitis B virus; HCV: hepatitis C virus; HDL: high-density lipoprotein; LAL: lysosomal acid lipase; LAL-D: lysosomal acid lipase deficiency; LDL: low-density lipoprotein; NGS: next-generation sequencing; ULN: upper limit of normal.
See this image and copyright information in PMC

References

    1. Reiner Z., Guardamagna O., Nair D., Soran H., Hovingh K., Bertolini S., Jones S., Coric M., Calandra S., Hamilton J., et al. Lysosomal acid lipase deficiency: An under-recognized cause of dyslipidaemia and liver dysfunction. Atherosclerosis. 2014;235:21–30. - PubMed
    1. Bernstein D.L., Hulkova H., Bialer M.G., Desnick R.J. Cholesteryl ester storage disease: Review of the findings in 135 reported patients with an underdiagnosed disease. J. Hepatol. 2013;58:1230–1243. - PubMed
    1. Jones S.A., Valayannopoulos V., Schneider E., Eckert S., Banikazemi M., Bialer M., Cederbaum S., Chan A., Dhawan A., Di Rocco M., et al. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet. Med. 2016;18:452–458. doi: 10.1038/gim.2015.108. - DOI - PMC - PubMed
    1. Strebinger G., Muller E., Feldman A., Aigner E. Lysosomal acid lipase deficiency—Early diagnosis is the key. Hepatic Med. 2019;11:79–88. - PMC - PubMed
    1. Balwani M., Balistreri W., D’Antiga L., Evans J., Ros E., Abel F., Wilson D.P. Lysosomal acid lipase deficiency manifestations in children and adults: Baseline data from an international registry. Liver Int. 2023;43:1537–1547. - PubMed

LinkOut - more resources