Abstract
Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (<1%). Three of the patients had novel mutations, one of them was a collodion baby and the other one was mistyped as type III due to its atypical presentation at the beginning and he was treated with ERT for 8 months. In this report, we present our type II Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type.
Similar content being viewed by others
References
Bove KE, Daugherty C, Grabowski GA (1995) Pathological findings in Gaucher disease type 2 patients following enzyme therapy. Hum Pathol 26(9):1040–1045
Chabás A, Gort L, Díaz-Font A, Montfort M, Santamaría R, Cidrás M, Grinberg D, Vilageliu L (2005) Perinatal lethal phenotype with generalized ichthyosis in a type 2 Gaucher disease patient with the [L444P;E326K]/P182L genotype: effect of the E326K change in neonatal and classic forms of the disease. Blood Cells Mol Dis 35(2):253–258
Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ, Zimran A (2000) The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160(18):2835–2843
Felderhoff-Mueser U, Uhl J, Penzel R, van Landeghem F, Vogel M, Obladen M, Kopitz J (2004) Intrauterine onset of acute neuropathic type 2 Gaucher disease: identification of a novel insertion sequence. Am J Med Genet A 128A(2):138–143
Lui K, Commens C, Chong R, Jaworski R (1988) Collodion babies with Gauchers disease. Arch Dis Child 63:854–856
Oberling C, Woringer P (1927) La maladie de Gaucher chez la nourisson. Rev Fr Pediatr 3:475–532
Saral S, Vural A, Wollenberg A, Ruzicka T (2017) A practical approach to ichthyoses with systemic manifestations. Clin Genet 91:799–812
Sidransky E, Sherer DM, Ginns EI (1992) Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene. Pediatr Res 32:494–498
Sidransky E, Fartasch M, Lee RE, Metlay LA, Abella S, Zimran A, Gao W, Elias PM, Ginns EI, Holleran WM (1996) Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease. Pediatr Res 39:134–141
Stone DL, van Diggelen OP, de Klerk JB et al (1999) Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease? Eur J Hum Genet 7(4):505–509
Stone DL, Tayebi N, Orvisky E, Stubblefield B, Madike V, Sidransky E (2000) Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease. Hum Mutat 15(2):181–188
Weiss K, Gonzalez AN, Lopez G, Pedoeim L, Groden C, Sidransky E (2015) The clinical management of type 2 Gaucher disease. Mol Genet Metab 114:110–122
Acknowledgements
• Details of the contributions of individual authors
Conception and design of the article: F.D. Bulut, D. Kör, B. Şeker-Yılmaz, Ö. Hergüner, S. Kılavuz, N. Önenli-Mungan
Draft of the article: F.D. Bulut, D. Kör, B. Şeker-Yılmaz, Ö. Hergüner, N. Önenli-Mungan
Definition of intellectual content: F.D. Bulut, D. Kör, N. Önenli-Mungan
Literature search: F.D. Bulut, B. Şeker-Yılmaz, S. Kılavuz, N. Önenli-Mungan
Data acquisition: F.D. Bulut, B. Şeker-Yılmaz, S. Ceylaner, F. Özkınay, S. Kılavuz
Data analysis: F.D. Bulut, S. Ceylaner, F. Özkınay, S. Kılavuz
Manuscript preparation: F.D. Bulut, D. Kör, B. Şeker-Yılmaz, S. Ceylaner, F. Özkınay, N. Önenli-Mungan
Manuscript editing: F.D. Bulut, D. Kör, S. Ceylaner, F. Özkınay, N. Önenli-Mungan
Manuscript review: F.D. Bulut, B. Şeker-Yılmaz, Ö. Hergüner, N. Önenli-Mungan
Guarantor: F.D. Bulut
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
There are no conflicts of interest.
Ethical approval
Ethical committee approval is not required for retrospective clinical studies.
Patient consent statements were obtained from all of the patients’ legal guardians, also for usage of patient pictures.
Informed consent
Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.
Additional information
Synopsis
Gaucher disease type II is a lethal, acute and progressive neurologic subtype with heterogeneous clinical findings; therefore, clinicians must be aware of different presentations of the disease. In this report, we would like to highlight the phenotypic heterogeneity of Gaucher disease type II and present three novel mutations.
Rights and permissions
About this article
Cite this article
Bulut, F.D., Kör, D., Şeker-Yılmaz, B. et al. Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey. Metab Brain Dis 33, 1223–1227 (2018). https://doi.org/10.1007/s11011-018-0236-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-018-0236-0