CESD: An under-recognised but important cause of fatty liver
Dear Editor,
Anstee et al (1) provided an excellent review of current practice in
investigating non-alcoholic fatty liver disease with a comprehensive
diagnostic algorithm. However, we feel that the "metabolic screen" should
include cholesterol ester storage disease (CESD), particularly now in
light of recent developments in treatment(2).
CESD is an autosomal recessive disorder caused by lysosomal acid
lipase (LAL) deficiency. In addition, complete absence of LAL activity
causes Wolman disease (3,4), which is fatal in early infancy. The onset
of CESD takes place during childhood or adolescence with variable clinical
presentation. Hepatomegaly, abnormal liver function tests and statin-
resistant hypercholesterolaemia are the main clinical findings however
several asymptomatic cases have been described. The prevalence of CESD in
the UK is currently unknown, but commonly quoted as 0.1/100,000 (5).
However, a more recent South-German population survey of common
heterozygous mutation carriers reports a higher prevalence of 2.5/100,000
(6), perhaps suggesting under-diagnosis. Diagnostic confirmation is by
measuring LAL activity in the leucocytes (2-8% of controls). This normally
requires 10ml of lithium heparin sample to be sent to a regional
enzymology laboratory.
We therefore suggest in addition to excluding alpha1-antitrypsin
deficiency, hereditary haemochromatosis and Wilson's disease; to consider
CESD as a differential diagnosis.
3. A Abramov, S Schorr and M Wolman, Generalized xanthomatosis with
calcified adrenals. Am J Dis Child 91 (1956), pp. 282-286
4. M Wolman, VV Sterk, S Gatt and M Frenkel , Primary familial
xanthomatosis with involvement and calcification of the adrenals: report
of two more cases in siblings of a previously described infant. Pediatrics
28 (1961), pp. 742-757
5. Assmann G, Seedorf U. Acid lipase deficiency: Wolman disease and
cholesterol ester storage disease. Sciver CR, Beuadet LA, Sly WS, Valle D.
The Metabolic & Molecular Bases of Inherited Disease (8th edition)
2001; 3551-3572. New York, McGraw-Hill
6. S. Muntoni, H. Wiebusch, M. Jansen-Rust, S. Rust, U. Seedorf, H.
Schulte, K. Berger, H. Funke and G. Assmann, Prevalence of Cholesteryl
Ester Storage Disease, Artrioscler. Thromb. Vasc. Biol. 27 (2007), pp.
1866-1868.
Rapid Response:
CESD: An under-recognised but important cause of fatty liver
Dear Editor,
Anstee et al (1) provided an excellent review of current practice in
investigating non-alcoholic fatty liver disease with a comprehensive
diagnostic algorithm. However, we feel that the "metabolic screen" should
include cholesterol ester storage disease (CESD), particularly now in
light of recent developments in treatment(2).
CESD is an autosomal recessive disorder caused by lysosomal acid
lipase (LAL) deficiency. In addition, complete absence of LAL activity
causes Wolman disease (3,4), which is fatal in early infancy. The onset
of CESD takes place during childhood or adolescence with variable clinical
presentation. Hepatomegaly, abnormal liver function tests and statin-
resistant hypercholesterolaemia are the main clinical findings however
several asymptomatic cases have been described. The prevalence of CESD in
the UK is currently unknown, but commonly quoted as 0.1/100,000 (5).
However, a more recent South-German population survey of common
heterozygous mutation carriers reports a higher prevalence of 2.5/100,000
(6), perhaps suggesting under-diagnosis. Diagnostic confirmation is by
measuring LAL activity in the leucocytes (2-8% of controls). This normally
requires 10ml of lithium heparin sample to be sent to a regional
enzymology laboratory.
We therefore suggest in addition to excluding alpha1-antitrypsin
deficiency, hereditary haemochromatosis and Wilson's disease; to consider
CESD as a differential diagnosis.
1.BMJ. 2011 Jul 18;343:d3897. doi: 10.1136/bmj.d3897
2.www.clinicaltrials.gov - ClinicalTrials.gov Identifier: NCT01307098
3. A Abramov, S Schorr and M Wolman, Generalized xanthomatosis with
calcified adrenals. Am J Dis Child 91 (1956), pp. 282-286
4. M Wolman, VV Sterk, S Gatt and M Frenkel , Primary familial
xanthomatosis with involvement and calcification of the adrenals: report
of two more cases in siblings of a previously described infant. Pediatrics
28 (1961), pp. 742-757
5. Assmann G, Seedorf U. Acid lipase deficiency: Wolman disease and
cholesterol ester storage disease. Sciver CR, Beuadet LA, Sly WS, Valle D.
The Metabolic & Molecular Bases of Inherited Disease (8th edition)
2001; 3551-3572. New York, McGraw-Hill
6. S. Muntoni, H. Wiebusch, M. Jansen-Rust, S. Rust, U. Seedorf, H.
Schulte, K. Berger, H. Funke and G. Assmann, Prevalence of Cholesteryl
Ester Storage Disease, Artrioscler. Thromb. Vasc. Biol. 27 (2007), pp.
1866-1868.
Competing interests: No competing interests