title: Senescent case of cholesterol ester storage disease that progressed to liver cirrhosis with a novel mutation (N250H) of lysosomal acid lipase gene.
abstract: 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 Kupffer 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.
authors.affiliation: Department of Gastroenterology, Tokai University Hachioji Hospital, Tokyo.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kojima
authors.forename: Norihito
authors.initials: N
authors.lastname: Watanabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Takashimizu
authors.forename: Tatehiro
authors.initials: T
authors.lastname: Kagawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Jun
authors.initials: J
authors.lastname: Koizumi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Tomoichi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamiguchi
authors.forename: Michio
authors.initials: M
authors.lastname: Tsuda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mine
keywords: cholesterol ester storage disease; human lysosomal acid lipase activity; human lysosomal acid lipase deficiency; laparoscopic findings; point mutation