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Novel mutation in a patient with cholesterol ester storage disease.

Lin P, Raikar S, Jimenez J, Conard K, Furuya KN - Case Rep Genet (2015)

Bottom Line: DNA sequencing confirmed the presence of a novel hepatic mutation.It is a four-nucleotide deletion c.57_60delTGAG in exon 2 of the LIPA gene.This mutation is predicted to result in a premature translation stop downstream of the deletion (p.E20fs) and, therefore, is felt to be a disease-causing mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA ; Thomas Jefferson University, Philadelphia, PA 19107, USA.

ABSTRACT
Cholesterol ester storage disease (CESD) is a chronic liver disease that typically presents with hepatomegaly. It is characterized by hypercholesterolemia, hypertriglyceridemia, high-density lipoprotein deficiency, and abnormal lipid deposition within multiple organs. It is an autosomal recessive disease that is due to a deficiency in lysosomal acid lipase (LAL) activity, which is coded by the lysosomal acid lipase gene (LIPA). We describe the case of a 5-year-old south Asian female incidentally found to have hepatomegaly, and subsequent workup confirmed the diagnosis of CESD. DNA sequencing confirmed the presence of a novel hepatic mutation. It is a four-nucleotide deletion c.57_60delTGAG in exon 2 of the LIPA gene. This mutation is predicted to result in a premature translation stop downstream of the deletion (p.E20fs) and, therefore, is felt to be a disease-causing mutation.

No MeSH data available.


Related in: MedlinePlus

(a) Liver biopsy, periodic acid-Schiff stain with diastase (magnification, ×40). Lipid demonstrated within the hepatocellular cytoplasm (arrows). (b) Electron micrograph (direct magnification, ×2500). The hepatocellular cytoplasm in places has a moth-eaten appearance with lipid droplets (arrows). Additionally, some foci show cholesterol crystals (∗) free in the hepatocellular cytoplasm.
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fig2: (a) Liver biopsy, periodic acid-Schiff stain with diastase (magnification, ×40). Lipid demonstrated within the hepatocellular cytoplasm (arrows). (b) Electron micrograph (direct magnification, ×2500). The hepatocellular cytoplasm in places has a moth-eaten appearance with lipid droplets (arrows). Additionally, some foci show cholesterol crystals (∗) free in the hepatocellular cytoplasm.

Mentions: On the basis of a clinical suspicion of a diagnosis of CESD, a liver biopsy was performed. It revealed diffuse, microvesicular steatosis in the hepatic parenchyma (Figure 2(a)). Portal tracts were expanded by foamy macrophages containing finely vacuolated material, which was periodic acid-Schiff positive and resistant to diastase digestion. Trichrome stain for collagen showed mild portal fibrosis with early delicate bridging fibrosis. Ultrastructurally, the cytoplasm had a moth-eaten appearance with the presence of lipid droplets and cholesterol crystals (Figure 2(b)). There was no evidence of hepatocellular necrosis, cholestasis, or bile duct proliferation.


Novel mutation in a patient with cholesterol ester storage disease.

Lin P, Raikar S, Jimenez J, Conard K, Furuya KN - Case Rep Genet (2015)

(a) Liver biopsy, periodic acid-Schiff stain with diastase (magnification, ×40). Lipid demonstrated within the hepatocellular cytoplasm (arrows). (b) Electron micrograph (direct magnification, ×2500). The hepatocellular cytoplasm in places has a moth-eaten appearance with lipid droplets (arrows). Additionally, some foci show cholesterol crystals (∗) free in the hepatocellular cytoplasm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4334435&req=5

fig2: (a) Liver biopsy, periodic acid-Schiff stain with diastase (magnification, ×40). Lipid demonstrated within the hepatocellular cytoplasm (arrows). (b) Electron micrograph (direct magnification, ×2500). The hepatocellular cytoplasm in places has a moth-eaten appearance with lipid droplets (arrows). Additionally, some foci show cholesterol crystals (∗) free in the hepatocellular cytoplasm.
Mentions: On the basis of a clinical suspicion of a diagnosis of CESD, a liver biopsy was performed. It revealed diffuse, microvesicular steatosis in the hepatic parenchyma (Figure 2(a)). Portal tracts were expanded by foamy macrophages containing finely vacuolated material, which was periodic acid-Schiff positive and resistant to diastase digestion. Trichrome stain for collagen showed mild portal fibrosis with early delicate bridging fibrosis. Ultrastructurally, the cytoplasm had a moth-eaten appearance with the presence of lipid droplets and cholesterol crystals (Figure 2(b)). There was no evidence of hepatocellular necrosis, cholestasis, or bile duct proliferation.

Bottom Line: DNA sequencing confirmed the presence of a novel hepatic mutation.It is a four-nucleotide deletion c.57_60delTGAG in exon 2 of the LIPA gene.This mutation is predicted to result in a premature translation stop downstream of the deletion (p.E20fs) and, therefore, is felt to be a disease-causing mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA ; Thomas Jefferson University, Philadelphia, PA 19107, USA.

ABSTRACT
Cholesterol ester storage disease (CESD) is a chronic liver disease that typically presents with hepatomegaly. It is characterized by hypercholesterolemia, hypertriglyceridemia, high-density lipoprotein deficiency, and abnormal lipid deposition within multiple organs. It is an autosomal recessive disease that is due to a deficiency in lysosomal acid lipase (LAL) activity, which is coded by the lysosomal acid lipase gene (LIPA). We describe the case of a 5-year-old south Asian female incidentally found to have hepatomegaly, and subsequent workup confirmed the diagnosis of CESD. DNA sequencing confirmed the presence of a novel hepatic mutation. It is a four-nucleotide deletion c.57_60delTGAG in exon 2 of the LIPA gene. This mutation is predicted to result in a premature translation stop downstream of the deletion (p.E20fs) and, therefore, is felt to be a disease-causing mutation.

No MeSH data available.


Related in: MedlinePlus