Introduction: Cholesteryl ester storage disease (CESD) is a rare recessive inborn error of lipid metabolism caused by mutations in the LIPA gene encoding the lysosomal acid lipase which hydrolyzes cholesteryl esters and triglycerides (TG) internalized via receptor-mediated endocytosis of plasma lipoprotein particles. As phenotipic expression variability, CESD sometimes may be underdiagnosed or diagnosed late in life. We recently characterized three novel patients affected by CESD. Case 1: 3.5-year-old italian female showing persistent liver enzymes elevation, hepatomegaly and combined hyperlipidemia. Blood examination showed: AST 78 UI/l, ALT 92 UI/l, TC 264 mg/dl, TG 178 mg/dl, HDL-C 31 mg/dl, ApoA 80 mg/dl, ApoB 132 mg/dl. Case 2: 7-year-old italian male with combined hyperlipidemia, low HDL-C levels and liver enzymes elevation. Blood examination showed: AST 44 UI/l, ALT 59 UI/l, TC 306 mg/dl, TG 173 mg/dl, HDL-C 34 mg/dl, ApoA 85 mg/dl, ApoB 186 mg/dl. Abdominal ultrasonography showed normal liver size with initial stage of periportal fibrosis. Case 3: 18-year-old italian male referred to our clinic after a liver biopsy, performed for hepatomegaly and liver enzymes elevation of unknown origin, which showed periportal fibrosis with foamy histiocytes, suggesting CESD diagnosis. Fasting lipid profile showed: TC 292 mg/dl, TG 148 mg/dl and HDL-C 39 mg/dl. Genetic analysis were performed by sequencing the LIPA gene: Case 1 and 3: both subjects resulted homozygous for LIPA gene mutation c.894 G>A in exon 8 (del p.S275_Q298) Case 2: the subject resulted heterozygous for LIPA gene mutation c.894 G>A (del p.S275_Q298) and c.883 C>T (p.H295Y) in exon 8. Conclusions: CESD should more often be considered, since childhood, as a differential diagnosis in liver diseases of unknown origin, when hypertransaminasemia and combined hyperlipidemia with low HDL cholesterol levels occur. Awareness of the disease and efficient diagnostic tools should facilitate the correct diagnosis and therapy.
Cholesteryl ester storage disese: experiences in pediatrics
ABELLO, Francesca;GUARDAMAGNA, Ornella
2011-01-01
Abstract
Introduction: Cholesteryl ester storage disease (CESD) is a rare recessive inborn error of lipid metabolism caused by mutations in the LIPA gene encoding the lysosomal acid lipase which hydrolyzes cholesteryl esters and triglycerides (TG) internalized via receptor-mediated endocytosis of plasma lipoprotein particles. As phenotipic expression variability, CESD sometimes may be underdiagnosed or diagnosed late in life. We recently characterized three novel patients affected by CESD. Case 1: 3.5-year-old italian female showing persistent liver enzymes elevation, hepatomegaly and combined hyperlipidemia. Blood examination showed: AST 78 UI/l, ALT 92 UI/l, TC 264 mg/dl, TG 178 mg/dl, HDL-C 31 mg/dl, ApoA 80 mg/dl, ApoB 132 mg/dl. Case 2: 7-year-old italian male with combined hyperlipidemia, low HDL-C levels and liver enzymes elevation. Blood examination showed: AST 44 UI/l, ALT 59 UI/l, TC 306 mg/dl, TG 173 mg/dl, HDL-C 34 mg/dl, ApoA 85 mg/dl, ApoB 186 mg/dl. Abdominal ultrasonography showed normal liver size with initial stage of periportal fibrosis. Case 3: 18-year-old italian male referred to our clinic after a liver biopsy, performed for hepatomegaly and liver enzymes elevation of unknown origin, which showed periportal fibrosis with foamy histiocytes, suggesting CESD diagnosis. Fasting lipid profile showed: TC 292 mg/dl, TG 148 mg/dl and HDL-C 39 mg/dl. Genetic analysis were performed by sequencing the LIPA gene: Case 1 and 3: both subjects resulted homozygous for LIPA gene mutation c.894 G>A in exon 8 (del p.S275_Q298) Case 2: the subject resulted heterozygous for LIPA gene mutation c.894 G>A (del p.S275_Q298) and c.883 C>T (p.H295Y) in exon 8. Conclusions: CESD should more often be considered, since childhood, as a differential diagnosis in liver diseases of unknown origin, when hypertransaminasemia and combined hyperlipidemia with low HDL cholesterol levels occur. Awareness of the disease and efficient diagnostic tools should facilitate the correct diagnosis and therapy.
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