Cholesteryl ester storage disease: endoscopic findings of an orphan disease

A 23-year-old man with normal antenatal history was admitted to hospital because of right hypochondrial pain, periodic nausea, and fatigue. The patient reported an episode of idiopathic jaundice with moderate fever 5 years previously. He was a non-smoker who did not drink alcohol nor take oral or intravenous drugs. Evaluation for viral hepatitis was negative. His physical examination revealed a high body mass index (BMI) of 32.2 kg/m², his liver was palpable 2 cm below the costal margin, but his spleen was nonpalpable. Laboratory test results showed a leukocytosis, as well as high levels of total bilirubin (29.2 µmol/L), conjugated bilirubin (7.7 µmol/L), AST (48 U/L), total cholesterol (7.58 mmol/L), triglycerides (1.82 mmol/L), LDL-C (5.29 mmol/L), and VLDL-C (0.83 mmol/L), but his HDL-C level was normal (0.67 mmol/L).

Abdominal ultrasonography showed hepatosplenomegaly with moderate diffuse parenchymal changes in the liver (liver steatosis) and pancreas. Arteriosclerotic vascular disease with hemodynamically relevant stenotic brachiocephalic vessels (20 % – 35 %) was found on brachiocephalic vessel ultrasonography. Upper gastrointestinal endoscopy revealed regions of flat yellow- and brown-speckled pigmented mucosa from the descending part of the duodenum to the fourth part ([Video 1]). Histopathological examination of a biopsy taken from the duodenal mucosa showed numerous macrophages containing brownish granules in their cytoplasm ([Fig. 1]). Staining of the specimen with Perlsʼ stain for iron-containing deposits was completely negative ([Fig. 2]).

Video 1 Upper gastrointestinal endoscopy showing regions of flat yellow- and brownish-speckled pigmented mucosa in the duodenum. The biopsy showed duodenal pseudomelanosis.

Fig. 1 Histopathological images from a biopsy of the duodenal mucosa stained by hematoxylin and eosin (H&E) showing numerous macrophages containing brownish granules in their cytoplasm, magnification: a × 100; b × 400.

Fig. 2 Histopathological image of the biopsy with Perls’ staining showing that the pigment was negative for iron-containing deposits.

An ultrasonography-guided liver biopsy was performed, the results of which revealed moderate histologic hepatitic activity, fibrous degeneration (grade 3), and severe steatosis with an accumulation of foam cells. Homozygosity for pSer103Arg +/0 IVS8 1G > A was found on genetic sequence analysis of the LIPA gene. Lysosomal acid lipase (LAL) deficiency cholesteryl ester storage disease (CESD) was confirmed.

LAL deficiency is a rare (orphan) autosomal recessive lysosomal lipid storage disorder caused by mutations in the LAL gene (LIPA), which is characterized by the accumulation of cholesteryl esters and triglycerides [1] [2]. Depending on the residual enzyme activity, two different presentations may be seen: an early-onset severe and lethal phenotype known as Wolman disease – absent or < 1 % of normal LAL activity – or a late-onset attenuated phenotype known as CESD – 1 % – 12 % of normal LAL activity [1] [2]. Over 40 LIPA mutations on chromosome 10q23.2-23.3 that cause CESD and Wolman disease have been identified [2] [3]. There have been 135 CESD patients described in the literature [4].

Endoscopy_UCTN_Code_CCL_1AB_2AZ_3AZ

Competing interests

None

• References

• 1 Pant M, Oshima K. Cholesteryl ester storage disease: An underdiagnosed cause of cirrhosis in adults. Ann Diagn Pathol 2017; 31: 66-70
• 2 Strebinger G, Müller E, Feldman A. et al. Lysosomal acid lipase deficiency – early diagnosis is the key. Hepat Med 2019; 11: 79-88
• 3 Stenson PD, Mort M, Ball EV. et al. The Human Gene Mutation Database: 2008 update. Genome Med 2009; 1: 13
• 4 Bernstein DL, Hülkova H, Bialer MG. et al. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol 2013; 58: 1230-1243