Pediatric Gastroenterology, Hepatology & Nutrition

  • 제20권4호
  • /
  • Pages.263-267
  • /
  • 2017
  • /
  • 2234-8646(pISSN)
  • /
  • 2234-8840(eISSN)
대한소아소화기영양학회 (The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition)
권호 표지
DOI QR코드

DOI QR Code

A Novel Homozygous LIPA Mutation in a Korean Child with Lysosomal Acid Lipase Deficiency

  • Kim, Kwang Yeon (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Ju Whi (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Lee, Kyung Jae (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Park, Eunhyang (Department of Pathology, Seoul National University College of Medicine) ;
  • Kang, Gyeong Hoon (Department of Pathology, Seoul National University College of Medicine) ;
  • Choi, Young Hun (Department of Radiology, Seoul National University College of Medicine) ;
  • Kim, Woo Sun (Department of Radiology, Seoul National University College of Medicine) ;
  • Ko, Jung Min (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Moon, Jin Soo (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Ko, Jae Sung (Department of Pediatrics, Seoul National University College of Medicine)
  • 투고 : 2016.10.01
  • 심사 : 2017.03.17
  • 발행 : 2017.12.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Patients with lysosomal acid lipase (LAL) deficiency and glycogen storage disease (GSD) demonstrated hepatomegaly 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 intracytoplasmic 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 enzymes 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 children with hepatosplenomegaly and dyslipidemia.

키워드

참고문헌

  1. Du H, Sheriff S, Bezerra J, Leonova T, Grabowski GA. Molecular and enzymatic analyses of lysosomal acid lipase in cholesteryl ester storage disease. Mol Genet Metab 1998;64:126-34. https://doi.org/10.1006/mgme.1998.2707
  2. Hoffman EP, Barr ML, Giovanni MA, Murray MF. Lysosomal acid lipase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al, eds. GeneReviews(R). Seattle (WA): University of Washington, 1993.
  3. Bernstein DL, Hulkova H, Bialer MG, Desnick RJ. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol 2013;58:1230-43. https://doi.org/10.1016/j.jhep.2013.02.014
  4. Heller S, Worona L, Consuelo A. Nutritional therapy for glycogen storage diseases. J Pediatr Gastroenterol Nutr 2008;47 Suppl 1:S15-21. https://doi.org/10.1097/MPG.0b013e3181818ea5
  5. Burton BK, Deegan PB, Enns GM, Guardamagna O, Horslen S, Hovingh GK, et al. Clinical features of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr 2015;61:619-25. https://doi.org/10.1097/MPG.0000000000000935
  6. Barker CC, Butzner JD, Woodman RC, Parsons HG. 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 2001;32: 197-200. https://doi.org/10.1097/00005176-200102000-00019
  7. Ko JS, Moon JS, Seo JK, Yang HR, Chang JY, Park SS. A mutation analysis of the AGL gene in Korean patients with glycogen storage disease type III. J Hum Genet 2007;59:42-5.
  8. Fujiyama J, Sakuraba H, Kuriyama M, Fujita T, Nagata K, Nakagawa H, et al. A new mutation (LIPA Tyr22X) of lysosomal acid lipase gene in a Japanese patient with Wolman disease. Hum Mutat 1996;8:377-80. https://doi.org/10.1002/(SICI)1098-1004(1996)8:4<377::AID-HUMU15>3.0.CO;2-#
  9. Kuranobu N, Murakami J, Okamoto K, Nishimura R, Murayama K, Takamura A, et al. Cholesterol ester storage disease with a novel LIPA mutation (L264P) that presented massive hepatomegaly: a case report. Hepatol Res 2016;46:477-82. https://doi.org/10.1111/hepr.12574
  10. Scott SA, Liu B, Nazarenko I, Martis S, Kozlitina J, Yang Y, et al. Frequency of the cholesteryl ester storage disease common LIPA E8SJM mutation (c.894G>A) in various racial and ethnic groups. Hepatology 2013; 58:958-65. https://doi.org/10.1002/hep.26327
  11. Burton BK, Balwani M, Feillet F, Baric I, Burrow TA, Camarena Grande C, et al. A phase 3 trial of Sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med 2015;373:1010-20. https://doi.org/10.1056/NEJMoa1501365
  12. Valayannopoulos V, Malinova V, Honzik T, Balwani M, Breen C, Deegan PB, et al. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency. J Hepatol 2014;61:1135-42. https://doi.org/10.1016/j.jhep.2014.06.022

피인용 문헌

  1. Large‐scale functional LIPA variant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency vol.40, pp.11, 2017, https://doi.org/10.1002/humu.23837