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Atherosclerosis. 2014 Jul;235(1):21-30. doi: 10.1016/j.atherosclerosis.2014.04.003. Epub 2014 Apr 15.

Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction.

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University Hospital Center, School of Medicine, University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. Electronic address:
Department of Public and Health Sciences, Medical School, University of Turin, Piazza Polonia 94, I-10126 Turin, Italy.
Department of Clinical Biochemistry, Royal Free Hospital NHS Foundation Trust, Pond Street, London NW3 2QG, UK.
Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK.
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, Netherlands.
Department of Internal Medicine, University of Genoa, Viale Benedetto XV n. 6, 16132 Genoa, Italy.
Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, St. Mary's Hospital, Oxford Road, Manchester M13 9WL, UK.
University Hospital Center, School of Medicine, University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Campi 287, I-41125 Modena, Italy.
Biochemistry Department, Yorkhill Hospital, Glasgow, G3 8SJ, UK.
Synageva BioPharma Corp., 33 Hayden Ave., Lexington, MA 02421, USA.
Lipid Clinic, Endocrinology & Nutrition Service, Institut d'Investigations Biomèdiques August Pi Sunyer, Hospital Clínic, C. Villarroel, 170, 08036 Barcelona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carloss III (ISCIII), Spain. Electronic address:


Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease caused by deleterious mutations in the LIPA gene. The age at onset and rate of progression vary greatly and this may relate to the nature of the underlying mutations. Patients presenting in infancy have the most rapidly progressive disease, developing signs and symptoms in the first weeks of life and rarely surviving beyond 6 months of age. Children and adults typically present with some combination of dyslipidaemia, hepatomegaly, elevated transaminases, and microvesicular hepatosteatosis on biopsy. Liver damage with progression to fibrosis, cirrhosis and liver failure occurs in a large proportion of patients. Elevated low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels are common features, and cardiovascular disease may manifest as early as childhood. Given that these clinical manifestations are shared with other cardiovascular, liver and metabolic diseases, it is not surprising that LAL-D is under-recognized in clinical practice. This article provides practical guidance to lipidologists, endocrinologists, cardiologists and hepatologists on how to recognize individuals with this life-limiting disease. A diagnostic algorithm is proposed with a view to achieving definitive diagnosis using a recently developed blood test for lysosomal acid lipase. Finally, current management options are reviewed in light of the ongoing development of enzyme replacement therapy with sebelipase alfa (Synageva BioPharma Corp., Lexington, MA, USA), a recombinant human lysosomal acid lipase enzyme.


Cholesteryl ester storage disease; Dyslipidaemia; Hepatomegaly; Lysosomal acid lipase deficiency; Wolman disease

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