A Novel Homozygous LIPA Mutation in a Korean Child with Lysosomal Acid Lipase Deficiency
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Patients with lysosomal acid lipase (LAL) deficiency and glycogen storage disease (GSD) demonstrated hep-atomegaly and dyslipidemia. In our case, a 6-year-old boy presented with hepatosplenomegaly. At 3 years of age, GSD had been diagnosed by liver biopsy at another hospital. He showed elevated serum liver enzymes and dyslipidemia. Liver biopsy revealed diffuse microvesicular fatty changes in hepatocytes, septal fibrosis and foamy macrophages. Ultrastructural examination demonstrated numerous lysosomes that contained lipid material and in-tracytoplasmic cholesterol clefts. A dried blood spot test revealed markedly decreased activity of LAL. LIPA gene sequencing identified the presence of a novel homozygous mutation (p.Thr177Ile). The patient’s elevated liver en-zymes and dyslipidemia improved with enzyme replacement therapy. This is the first report of a Korean child with LAL deficiency, and our findings suggest that this condition should be considered in the differential diagnosis of chil-dren with hepatosplenomegaly and dyslipidemia.
Abstract
Patients with lysosomal acid lipase (LAL) deficiency and glycogen storage disease (GSD) demonstrated hep-atomegaly and dyslipidemia. In our case, a 6-year-old boy presented with hepatosplenomegaly. At 3 years of age, GSD had been diagnosed by liver biopsy at another hospital. He showed elevated serum liver enzymes and dyslipidemia. Liver biopsy revealed diffuse microvesicular fatty changes in hepatocytes, septal fibrosis and foamy macrophages. Ultrastructural examination demonstrated numerous lysosomes that contained lipid material and in-tracytoplasmic cholesterol clefts. A dried blood spot test revealed markedly decreased activity of LAL. LIPA gene sequencing identified the presence of a novel homozygous mutation (p.Thr177Ile). The patient’s elevated liver en-zymes and dyslipidemia improved with enzyme replacement therapy. This is the first report of a Korean child with LAL deficiency, and our findings suggest that this condition should be considered in the differential diagnosis of chil-dren with hepatosplenomegaly and dyslipidemia.
참고문헌 (12)
- Du H, "Molecular and enzymatic analyses of lysosomal acid lipase in cholesteryl ester storage disease", Mol Genet Metab, 64, pp.126~134 (1998)
- Hoffman EP, "GeneReviews(R)" (1993), University of Washington
- Bernstein DL, "Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease", J Hepatol, 58, pp.1230~1243 (2013)
- Heller S, "Nutritional therapy for glycogen storage diseases", J Pediatr Gastroenterol Nutr, 47(Suppl 1), pp.S15~S21 (2008)
- Burton BK, "Clinical features of lysosomal acid lipase deficiency", J Pediatr Gastroenterol Nutr, 61, pp.619~625 (2015)
- Barker CC, "Crohn-like enteritis presenting as hypoglycemia in a patient with glycogen storage disease type 1b, treated with granulocyte colony-stimulating factor and splenectomy", J Pediatr Gastroenterol Nutr, 32, pp.197~200 (2001)
- Ko JS, "A mutation analysis of the AGL gene in Korean patients with glycogen storage disease type III", J Hum Genet, 59, pp.42~45 (2007)
- Fujiyama J, "A new mutation (LIPA Tyr22X) of lysosomal acid lipase gene in a Japanese patient with Wolman disease", Hum Mutat, 8, pp.377~380 (1996)
- Kuranobu N, "Cholesterol ester storage disease with a novel LIPA mutation (L264P) that presented massive hepatomegaly: a case report", Hepatol Res, 46, pp.477~482 (2016)
- Scott SA, "Frequency of the cholesteryl ester storage disease common LIPA E8SJM mutation (c.894G＞A) in various racial and ethnic groups", Hepatology, 58, pp.958~965 (2013)
- Burton BK, "A phase 3 trial of Sebelipase alfa in lysosomal acid lipase deficiency", N Engl J Med, 373, pp.1010~1020 (2015)
- Valayannopoulos V, "Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency", J Hepatol, 61, pp.1135~1142 (2014)