Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1391-1394
Number of pages4
JournalEuropean Journal of Pediatrics
Volume173
Issue number10
DOIs
Publication statusPublished - Sep 12 2014

Fingerprint

Wolman Disease
Hemophagocytic Lymphohistiocytosis
Cholesterol Esters
Lysosomes
Triglycerides
Inflammasomes
Sterol Esterase
Gaucher Disease
Inborn Errors Metabolism
Failure to Thrive
Macrophage Activation
Enzymes
Jaundice
Coinfection
Thrombocytopenia
Vomiting
Anemia
Diarrhea
Hydrolysis
Pediatrics

Keywords

  • Cholesterol crystal
  • Hemophagocytic lymphohistiocytosis
  • Inflammasome
  • Wolman disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Wolman disease associated with hemophagocytic lymphohistiocytosis : attempts for an explanation. / Taurisano, Roberta; Maiorana, Arianna; De Benedetti, Fabrizio; Dionisi-Vici, Carlo; Boldrini, Renata; Deodato, Federica.

In: European Journal of Pediatrics, Vol. 173, No. 10, 12.09.2014, p. 1391-1394.

Research output: Contribution to journalArticle

@article{e775dc4b582a41aa9afe760b9893529f,
title = "Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation",
abstract = "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.",
keywords = "Cholesterol crystal, Hemophagocytic lymphohistiocytosis, Inflammasome, Wolman disease",
author = "Roberta Taurisano and Arianna Maiorana and {De Benedetti}, Fabrizio and Carlo Dionisi-Vici and Renata Boldrini and Federica Deodato",
year = "2014",
month = "9",
day = "12",
doi = "10.1007/s00431-014-2338-y",
language = "English",
volume = "173",
pages = "1391--1394",
journal = "European Journal of Pediatrics",
issn = "0340-6199",
publisher = "Springer Berlin Heidelberg",
number = "10",

}

TY - JOUR

T1 - Wolman disease associated with hemophagocytic lymphohistiocytosis

T2 - attempts for an explanation

AU - Taurisano, Roberta

AU - Maiorana, Arianna

AU - De Benedetti, Fabrizio

AU - Dionisi-Vici, Carlo

AU - Boldrini, Renata

AU - Deodato, Federica

PY - 2014/9/12

Y1 - 2014/9/12

N2 - 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.

AB - 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.

KW - Cholesterol crystal

KW - Hemophagocytic lymphohistiocytosis

KW - Inflammasome

KW - Wolman disease

UR - http://www.scopus.com/inward/record.url?scp=84918830930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918830930&partnerID=8YFLogxK

U2 - 10.1007/s00431-014-2338-y

DO - 10.1007/s00431-014-2338-y

M3 - Article

C2 - 24844354

AN - SCOPUS:84918830930

VL - 173

SP - 1391

EP - 1394

JO - European Journal of Pediatrics

JF - European Journal of Pediatrics

SN - 0340-6199

IS - 10

ER -