Journal List > J Korean Ophthalmol Soc > v.54(1) > 1009466

TOOLS
Lee, Kim, Jeong, and Hwang: Ocular Abnormality of Korean Patients with Molecular Genetically Confirmed Gaucher Disease
Original Article

J Korean Ophthalmol Soc 2013;54(1):131-135.

Published online: 25 September 2013

DOI: https://doi.org/10.3341/jkos.2013.54.1.131

Ocular Abnormality of Korean Patients with Molecular Genetically Confirmed Gaucher Disease

Sangmoon Lee, MD1, Hyon J. Kim, MD2, Seon-Yong Jeong, PhD2, Jeong-Min Hwang, MD1,

1Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

2Department of Medical Genetics, Ajou University School of Medicine, Suwon, Korea

Address reprint requests to Jeong-Min Hwang, MD Department of Ophthalmology, Seoul National University Bundang Hospital #82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 463-707, Korea Tel: 82-31-787-7372, Fax: 82-31-787-4057, E-mail: hjm@snu.ac.kr

Received 28 November 2011       Accepted 31 January 2012

Copyright © 2013 Korean Ophthalmological Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To investigate the ophthalmologic manifestations of Korean patients with Gaucher disease.

Methods

Clinical records of 5 patients who were referred to the pediatric ophthalmology clinic of Seoul National University Bundang Hospital after diagnosis of Gaucher disease at the genetics clinic of Ajou University Hospital between 2007 and 2008 were retrospectively reviewed.

Results

Five patients with type 3 Gaucher disease had hepatosplenomegaly and oculomotor apraxia, and 4 patients had growth and developmental delay. The most commonly detected genetic mutation was L444P. In addition, P201H, F2131, R257Q, and D315E+Rec 1b were identified. Five patients had oculomotor apraxia and limitation of abduction, and 4 patients had esotropia. One of the 4 patients who showed combined limitation of abduction, oculomotor apraxia, and esotropia, yet did not have growth and developmental delay.

Conclusions

Most of the patients who were referred for ocular motor abnormalities with Gaucher disease showed a limitation of abduction, oculomotor apraxia, and esotropia. In patients with a limitation of abduction, oculomotor apraxia, and esotropia, Gaucher disease should be considered. Ophthalmologic examination is essential for subtyping and prognosing Gaucher disease.

Keywords: Esotropia, Gaucher disease, Lysosomal storage disease, Neuropathy, Oculomotor apraxia

References

1. Brady RO, Kanfer JN, Bradley RM, Shapiro D. Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease. J Clin Invest. 1966; 45:1112–5.
crossref
2. Sidransky E. Gaucher disease: complexity in a “simple” disorder. Mol Genet Metab. 2004; 83:6–15.
crossref
3. Futerman AH, van Meer G. The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol. 2004; 5:554–65.
crossref
4. Futerman AH, Zimran A. Gaucher disease. Boca Raton: CRC/ Taylor & Francis;2006. p. 175–96.
5. Wong K, Sidransky E, Verma A, et al. Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab. 2004; 82:192–207.
crossref
6. Ida H, Rennert OM, Kawame H, et al. Mutation screening of 17 Japanese patients with neuropathic Gaucher disease. Hum Genet. 1996; 98:167–71.
crossref
7. Jeong SY, Park SJ, Kim HJ. Clinical and genetic characteristics of Korean patients with Gaucher disease. Blood Cells Mol Dis. 2011; 46:11–4.
crossref
8. Kim HJ, Kang IJ, Kim HS, et al. Korean gaucher disease patient registry. Korean J Pediatr Hematol Oncol. 1998; 5:44–53.
9. Choi HS, Kim SH, Ida H, Kim HJ. The clinical characteristics and gene analysis of Korean Gaucher disease with central nervous abdominal involvement. J Korean Pediatr Soc. 2000; 43:611–8.
10. Goker-Alpan O, Schiffmann R, Park JK, et al. Phenotypic con-tinuum in neuronopathic gaucher disease: an intermediate phenotype between type 2 and type 3. J Pediatr. 2003; 143:273–6.
crossref
11. Beutler E, Gelbart T, West C. Identification of six new Gaucher abdominal mutations. Genomics. 1993; 15:203–5.
12. Sinclair G, Choy FY, Ferreira P. Heterologous expression and abdominal of a rare Gaucher disease mutation (c.481C > T) from a Canadian aboriginal population using archival tissue samples. Mol Genet Metab. 2001; 74:345–52.
13. Yee RD, Purvin VA. Acquired ocular motor apraxia after aortic surgery. Trans Am Ophthalmol Soc. 2007; 105:152–8. discussion 158–9.
14. Leigh RJ, Zee DS. The neurology of eye movements. 4th ed.New York: Oxford University Press;2006. p. 108–87.
15. Harris CM, Taylor DS, Vellodi A. Ocular motor abnormalities in Gaucher disease. Neuropediatrics. 1999; 30:289–93.
crossref
16. Gross-Tsur V, Har-Even Y, Gutman I, Amir N. Oculomotor abdominal: the presenting sign of Gaucher disease. Pediatr Neurol. 1989; 5:128–9.
17. Mignot C, Doummar D, Maire I, De Villemeur TB. Type 2 Gaucher disease: 15 new cases and review of the literature. Brain Dev. 2006; 28:39–48.
crossref
18. Benko W, Ries M, Wiggs EA, et al. The saccadic and neurological deficits in type 3 Gaucher disease. PLoS One. 2011; 6:e22410.
crossref
19. Yee RW. The effect of drop vehicle on the efficacy and side effects of topical glaucoma therapy: a review. Curr Opin Ophthalmol. 2007; 18:134–9.
crossref
20. Beutler E, Grabowski GA. Gaucher Disease. Scriver CR, Sly WS, Childs B, editors. Metabolic and molecular bases of in-herited disease. 8th ed.Columbus: McGraw-Hill Inc;2001. 2.
21. Meivar-Levy I, Horowitz M, Futerman AH. Analysis of glucocere-brosidase activity using N-(1-[14C]hexanoyl)-D-erythroglucosyl-sphingosine demonstrates a correlation between levels of residual enzyme activity and the type of Gaucher disease. Biochem J. 1994; 303(Pt 2):377–82.
crossref
22. Grabowski GA. Gaucher disease: gene frequencies and geno-type/phenotype correlations. Genet Test. 1997; 1:5–12.
crossref
23. Hruska KS, LaMarca ME, Scott CR, Sidransky E. Gaucher abdominal: mutation and polymorphism spectrum in the glucocere-brosidase gene (GBA). Hum Mutat. 2008; 29:567–83.
24. Kawame H, Maekawa K, Eto Y. Molecular screening of Japanese patients with Gaucher disease: phenotypic variability in the same genotypes. Hum Mutat. 1993; 2:362–7.
crossref
25. Eto Y, Ida H. Clinical and molecular characteristics of Japanese Gaucher disease. Neurochem Res. 1999; 24:207–11.
26. Zhao H, Keddache M, Bailey L, et al. Gaucher's disease: abdominal of novel mutant alleles and genotype-phenotype relationships. Clin Genet. 2003; 64:57–64.
27. Jmoudiak M, Futerman AH. Gaucher disease: pathological abdominal and modern management. Br J Haematol. 2005; 129:178–88.

Table 1.
Summary of Gaucher disease patients
No Sex Phenotype Genotype Age at diagnosis Age at exam Age at surgery Age at death VOD VOS Nsc D/V Oculomotor apraxia
1 F Type 3 F2131/R257Q 10 mons 16 mons   30 mons poor FF poor FF Ortho L) abd −1 Present
2 F Type 3 L444P/P201H 14 mons 19 mons   23 mons poor FF poor FF 40 ET by K B) abd −4 Present
3 M Type 3 F2131/D315E+ Rec 1b 11 mons 27 mons     FF FF 30–35 E(T) by K R) abd −2 Present
4 M Type 3 L444/L444P 12 mons 59 mons     0.7 0.7 40 ET by K R) abd −2 L) abd −1 Present
5 M Type 3 L444/L444P 16 mons 18 mons 32 mons   FF FF 18 ET L) abd −0.5 Present

abd = abduction; D/V = ductions and versions; ET = esotropia; E(T) = intermittent esotropia; F = female; FF = fix and follow; K = Krimsky method; M = male; mons = months; Nsc = near without correction; ortho = orthotropia.

TOOLS
Similar articles