Novel Mutation in a Patient with Cholesterol Ester Storage Disease

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.

Living-Donor Liver Transplantation for Late-Onset Lysosomal Acid Lipase Deficiency

“…The clinical features of LAL deficiency include Hepatomegaly/hepatosplenomegaly, liver fibrosis, elevated serum transaminases (AST, ALT, or both), cirrhosis, atherosclerosis with a risk of stroke, heart disease and aneurysms (4). In addition, patients with LAL-deficiency may experience gastrointestinal symptoms including diarrhea, abdominal pain, and malabsorption (5) The metabolic consequences of this disorder tend to be mild. Most patients have elevated total cholesterol with elevated LDL level and low HDL levels (6).…”