Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation.

Eur J Pediatr 2014 Oct 21;173(10):1391-4. Epub 2014 May 21.

Division of Metabolism, Department of Pediatric Medicine, Bambino Gesu' Children's Hospital, IRCCS, Piazza S. Onofrio 4, Rome, 00165, Italy.

Unlabelled: The lysosomal acid lipase (LAL) is the enzyme responsible of the hydrolysis of cholesteryl esters and triglycerides within endo-lysosomes. Loss of enzyme activity leads to accumulation of cholesteryl esters and triglycerides in the lysosome of most tissues. The complete deficiency of LAL is responsible of Wolman disease (WD), a severe systemic disease manifesting in the first days of life with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, jaundice, anemia, and thrombocytopenia. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition which may be genetically determined or secondary to infections, malignancies, immune deficiencies, and rheumatologic disorders. So far, some inborn errors of metabolism have been associated with HLH (e.g., lysinuric protein intolerance, Gaucher's disease), and it has been anecdotally described in three WD patients, without any specific pathogenetic hypothesis. Here, we report on a WD patient, showing clear clinical, biochemical, and histological features indicative of HLH. We discuss the pathophysiological role of cholesteryl ester-induced inflammasome activation in macrophages, leading to a secondary HLH.

Conclusion: This case indicates that WD can cause secondary HLH and suggests that a careful metabolic workup should be performed when facing to a pediatric patient with HLH.

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http://link.springer.com/10.1007/s00431-014-2338-y
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http://dx.doi.org/10.1007/s00431-014-2338-yDOI Listing
October 2014
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