Cholesteryl Ester Storage Disease: CaseReport During Childhood

ZUHAL AKCOREN,1* SAFIYE GOGUS,1 NURTEN KOCAK,2 FIGEN GURAKAN,2HASAN OZEN,2 AND AYSEL YUCE2

1Pediatric Pathology Unit, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey2Pediatric Gastroenterology Unit, Hacettepe University Children’s Hospital, 06100 Ankara, Turkey

Received April 3, 1998; accepted December 21, 1998.

ABSTRACTCholesteryl ester storage disease (CESD) is rare andcharacterized by accumulation of cholesteryl esters andtriglycerides in many tissues due to the deficiency oflysosomal acid lipase. We report a 31⁄2-year-old child withCESD. The diagnosis was indicated by liver biopsy andconfirmed by reduced acid lipase activity in leukocytes.

Key words: cholesteryl ester storage disease, lysosomalacid lipase, liver biopsy

INTRODUCTIONCholesteryl ester storage disease (CESD) is a rareinborn error of metabolism characterized by accu-mulation of cholesteryl esters and triglycerides inmany tissues due to the deficiency of lysosomalacid lipase [1]. Clinically, it is manifested primarilyby hepatomegaly and hypercholesterolemia. Wol-man disease is the fatal infantile form of acid lipasedeficiency. CESD is a more benign form and mildcases may not be apparent until adolescence oradulthood. Both clinical conditions are inherited asautosomal recessive disorders. The gene encodinglysosomal acid lipase was mapped to chromosome10q23.2-q23.3 [2]. Different mutations were associ-ated with these two allelic disorders [3–6]. Since itis rarely seen and demonstrated by liver biopsy, wewish to report the clinical and liver biopsy findingsof a child with CESD.

CASE REPORTA 31⁄2-year-old girl was found to have elevated

serum transaminase levels during evaluation of

fever and was referred to Hacettepe University

Children’s Hospital for further investigation.

She was the second child of nonconsanguine-

ous healthy parents and her brother was also

healthy. Physical examination was unremarkable

besides hepatosplenomegaly, 4 and 1 cm below the

right and left costal margins, respectively. Labora-

tory investigation revealed Hb 13.6 g/dl, white

blood count (WBC) 9000/mm3, serum glutamic-

oxaloacetic transaminase (SGOT) 89 IU/L, serum

glutamic-pyruvic transaminase (SGPT) 102 IU/L,

cholesterol 356 mg/dl (N 5 145–270), triglycerides

225 mg/dl (N 5 30–160), low-density lipoprotein

(LDL) 266 mg/dl (N 5 0–155), and normal levels of

high-density lipoprotein (HDL) and very-low-

density lipoprotein (VLDL). An abdominal ultraso-

nography revealed parenchymal liver disease and

no adrenal calcification. A needle liver biopsy was

performed for diagnostic aids.

The liver biopsy sample was orange-yellow in

color and parenchymal cells were all enlarged and

vacuolated, producing a mosaic pattern on routine

histological examination (Fig. 1). Portal fibrosis

with some increase around clusters of hepatocytes

was present. Frozen sections under polarized light

showed diffuse, numerous aggregates of birefrin-*Corresponding author

Pediatric and Developmental Pathology 2, 574–576, 1999 Pediatric and Developmental Pathology

r1999 Society for Pediatric Pathology

gent crystals in parenchymal cells (Fig 2A,B).These cells were stained partially positive by oilred-O. These findings were consistent with CESDand cholestyramine theraphy was given to thepatient.

The acid lipase level studied in leukocytes wasfound to be low, 22 U (N 5 300–1000 U). The assaywas carried out using 4-methylumbelliferyl-palmi-tate as substrate in the presence of Triton X-100and with the activator cardiolipin [7].

DISCUSSIONCESD is rarely and mostly co-accidentally recog-nized in childhood during routine examination.Hepatomegaly with or without splenomegaly, hyper-tension due to premature atherosclerosis, or symp-toms due to liver cirrhosis may be the initial signs.Commonly it is diagnosed during adolescence orearly adulthood. This was the first case of ourPediatric Pathology Department in the last 20years.

On routine histologic examination, CESD maybe confused with glycogenosis. In both disordershepatomegaly and hyperlipidemia without splenicenlargement may appear in a child as in our casewith otherwise unremarkable mental and physicaldevelopment. Clinically massive hepatomegaly canbe misdiagnosed as glycogenosis type 1. Heat-sensitive birefringent crystals seen in frozen livertissue is highly suggestive for CESD and is notobserved in other lysosomal disorders. The orange-yellow color of the liver tissue may indicate thediagnosis. Hematoxylin-eosin sections may not re-flect the high lipid content seen in frozen tissue.Thus, we wish to emphasize the importance offrozen sections in addition to the routine proce-dure.

Accumulation of cholesteryl esters and triglyc-erides is seen mostly in liver and may be seen inspleen, bone marrow, and adrenals. Lipid storagein some other tissues, such as intestinal mucosa,interstitium of lung, renal glomeruli, and lympho-cytes, is more discrete. Although adrenal calcifica-tion is accepted as a characteristic sign of Wolmandisease, there have been rare cases of CESD withadrenal calcification [8]. Low-acid lipase activitycan be demonstrated in leukocytes and culturedskin fibroblasts as well as in liver tissue [1,8,9].Some different mutations were detected in patientswith CESD [3–6]. In all cases hepatomegaly in-creases with time, leads to hepatic fibrosis, andliver failure [1].

Although there is no specific treatment forCESD, significant reduction in plasma cholesterol,

Figure 1. Liver biopsy showing enlarged and vacu-olated hepatocytes producing a mosaic pattern. H & E,3132.Figure 2. A: Aggregates of birefringent crystals inhepatocytes. Frozen section, oil red-O, 3132. B: Birefrin-gent crystals under polarized light. Frozen section, 366.

CHOLESTERYL ESTER STORAGE 575

triglycerides, and LDL, and some decrease in liverenlargement were detected in patients treated with3-hydroxy 3-methylglutaryl CoA reductase inhibi-tor, e.g., lovastatin [10,11]. Liver transplantationmay be another form of treatment [12]. Prenataldiagnosis of CESD is possible by quantitative as-says and electrophoresis of lysosomal acid lipase incultured amniotic fluid cells [13].

ACKNOWLEDGMENTS

The authors thank Guy Besley, Ph.D., and WillinkBiochemical Genetics Unit, Royal Manchester Chil-dren’s Hospital, Pendlebury, Manchester M27 4HA,UK, for their help in assaying acid lipase level inleukocytes.

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