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Senescent case of cholesterol ester storage disease that progressed to liver cirrhosis with a novel mutation ( N250H ) of lysosomal acid lipase gene
Author(s) -
Kojima Seiichiro,
Watanabe Norihito,
Takashimizu Shinji,
Kagawa Tatehiro,
Shiraishi Koichi,
Koizumi Jun,
Hirabayashi Kenichi,
Ohkubo Tomoichi,
Kamiguchi Hiroshi,
Tsuda Michio,
Mine Tetsuya
Publication year - 2013
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12087
Subject(s) - lipid droplet , cirrhosis , lysosomal storage disease , spleen , lipase , pathology , liver biopsy , liver disease , medicine , chemistry , biology , biochemistry , biopsy , enzyme
The patient, a 69‐year‐old man, had a chief complaint of hepatomegaly. The liver was palpated four fingerbreadths below the costal margin, and the spleen was three fingerbreadths below the costal margin. There were no other abnormal findings. Laparoscopy showed that the liver resembled an orange‐yellow crayon in appearance and was nodular. The pathological findings of the liver biopsy tissue were consistent with liver cirrhosis. Inside the fibrous septum was an apparent aggregation of enlarged macrophages that phagocytosed lipid components, as well as enlarged K upffer cells that phagocytosed lipid droplets. Electron microscopy showed the lipid droplets to have a moth‐eaten appearance. Using monocytes extracted from the peripheral blood, acid lipase activity was measured by fluorescence spectrometry using 4‐methylumbelliferone palmitate as a substrate. This patient's human lysosomal acid lipase activity was 0.020 nM/min per 10 6 cells, corresponding to 5.9% of that in healthy subjects (0.332 ± 0.066 nM/min per 10 6 cells). Cholesterol ester storage disease was therefore diagnosed. The acid lipase A base sequence obtained from leukocytes by direct sequencing was compared with a library. This patient had a point mutation of N250H/N250H in exon 7, a novel gene abnormality that has not previously been reported.