Abstract
Gaucher disease type 2 is the most progressive and the rarest form of Gaucher disease, defined as the acute neuronopathic type. We presented two GD2 patients who died before three months of age due to severe septicemia, respiratory and liver failure. One was homozygous for a novel GBA variant c.590 T > A (p.197 K), and the second homozygous for the known GBA mutation c.1505G > A (p.R502H). Ichthyosis, hydrops fetalis, apnea, myoclonic seizures, and hepatosplenomegaly occurred in both patients, but hypertrophic cardiomyopathy was observed only in the second and unilateral cataract in the first patient. Due to the disease’s early and rapid neurological progression, we did not administer ERT to our patients. It is strongly believed that early diagnosis is essential, and prenatal diagnosis makes genetic counselling possible for future pregnancies.
This is a preview of subscription content, log in via an institution to check access.
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Akdag A, Oguz SS, Ezgu F, Erdeve O, Uras N, Dilmen U (2011) A newborn case with perinatal-lethal Gaucher disease due to R463H homozygosity complicated by C677T homozygosity in the MTHFR gene. J Pediatr Endocrinol Metab 24(5-6):381–383. https://doi.org/10.1515/jpem.2011.001
Alfonso P, Aznarez S, Giralt M, Pocovi M, Giraldo P, Spanish Gaucher's Disease, R (2007) Mutation analysis and genotype/phenotype relationships of Gaucher disease patients in Spain. J Hum Genet 52(5):391–396. https://doi.org/10.1007/s10038-007-0135-4
BenHamida E, Ayadi I, Ouertani I, Chammem M, Bezzine A, BenTmime R et al (2015) Perinatal-lethal Gaucher disease presenting as hydrops fetalis. Pan Afr Med J 21:110. https://doi.org/10.11604/pamj.2015.21.110.7052
Bronstein S, Karpati M, Peleg L (2014) An update of Gaucher mutations distribution in the Ashkenazi Jewish population: prevalence and country of origin of the mutation R496H. Isr Med Assoc J 16(11):683–685 Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25558695
Bulut FD, Kor D, Seker-Yilmaz B, Herguner O, Ceylaner S, Ozkinay F et al (2018) Four Gaucher disease type II patients with three novel mutations: a single Centre experience from Turkey. Metab Brain Dis 33(4):1223–1227. https://doi.org/10.1007/s11011-018-0236-0
Campbell PE, Harris CM, Harris CM, Sirimanna T, Vellodi A (2003) A model of neuronopathic Gaucher disease. J Inherit Metab Dis 26(7):629–639. https://doi.org/10.1023/b:boli.0000005619.14180.5c
Daykin EC, Ryan E, Sidransky E (2021) Diagnosing neuronopathic Gaucher disease: new considerations and challenges in assigning Gaucher phenotypes. Mol Genet Metab 132(2):49–58. https://doi.org/10.1016/j.ymgme.2021.01.002
Eblan MJ, Goker-Alpan O, Sidransky E (2005) Perinatal lethal Gaucher disease: a distinct phenotype along the neuronopathic continuum. Fetal Pediatr Pathol 24(4-5):205–222. https://doi.org/10.1080/15227950500405296
Grace ME, Balwani M, Nazarenko I, Prakash-Cheng A, Desnick RJ (2007) Type 1 Gaucher disease: null and hypomorphic novel chitotriosidase mutations-implications for diagnosis and therapeutic monitoring. Hum Mutat 28(9):866–873. https://doi.org/10.1002/humu.20524
Haverkaemper S, Marquardt T, Hausser I, Timme K, Kuehn T, Hertzberg C, Rossi R (2011) Congenital ichthyosis in severe type II Gaucher disease with a homozygous null mutation. Neonatology 100(2):194–197. https://doi.org/10.1159/000324116
Inui K, Yanagihara K, Otani K, Suzuki Y, Akagi M, Nakayama M et al (2001) A new variant neuropathic type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules. J Pediatr 138(1):137–139. https://doi.org/10.1067/mpd.2001.109789
Kooper AJ, Janssens PM, de Groot AN, Liebrand-van Sambeek ML, van den Berg CJ, Tan-Sindhunata GB, ..., Wevers RA (2006) Lysosomal storage diseases in non-immune hydrops fetalis pregnancies. Clin Chim Acta 371(1-2): 176–182. https://doi.org/10.1016/j.cca.2006.03.007
Koprivica V, Stone DL, Park JK, Callahan M, Frisch A, Cohen IJ et al (2000) Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Am J Hum Genet 66(6):1777–1786. https://doi.org/10.1086/302925
Lui K, Commens C, Choong R, Jaworski R (1988) Collodion babies with Gaucher's disease. Arch Dis Child 63(7):854–856. https://doi.org/10.1136/adc.63.7.854
Migita M, Hamada H, Fujimura J, Watanabe A, Shimada T, Fukunaga Y (2003) Glucocerebrosidase level in the cerebrospinal fluid during enzyme replacement therapy--unsuccessful treatment of the neurological abnormality in type 2 Gaucher disease. Eur J Pediatr 162(7-8):524–525. https://doi.org/10.1007/s00431-001-0859-7
Mignot C, Gelot A, Bessieres B, Daffos F, Voyer M, Menez F et al (2003) Perinatal-lethal Gaucher disease. Am J Med Genet A 120A(3):338–344. https://doi.org/10.1002/ajmg.a.20117
Nagappa M, Bindu PS, Taly AB, Sinha S (2015) Oculomotor apraxia in Gaucher disease. Pediatr Neurol 52(4):468–469. https://doi.org/10.1016/j.pediatrneurol.2014.10.016
Pastores GM, Hughes DA (1993) Gaucher Disease. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A (eds) GeneReviews((R)), Seattle (WA)
Plakkal N, Soraisham AS, Jirapradittha J, Pinto-Rojas A (2011) Perinatal lethal Gaucher disease. Indian J Pediatr 78(1):106–108. https://doi.org/10.1007/s12098-010-0247-2
Roshan Lal T, Sidransky E (2017) The Spectrum of neurological manifestations associated with Gaucher disease. Diseases 5(1). https://doi.org/10.3390/diseases5010010
Roshan Lal T, Seehra GK, Steward AM, Poffenberger CN, Ryan E, Tayebi N et al (2020) The natural history of type 2 Gaucher disease in the 21st century: a retrospective study. Neurology 95(15):e2119–e2130. https://doi.org/10.1212/WNL.0000000000010605
Staretz-Chacham O, Lang TC, LaMarca ME, Krasnewich D, Sidransky E (2009) Lysosomal storage disorders in the newborn. Pediatrics 123(4):1191–1207. https://doi.org/10.1542/peds.2008-0635
Stone DL, Carey WF, Christodoulou J, Sillence D, Nelson P, Callahan M et al (2000a) Type 2 Gaucher disease: the collodion baby phenotype revisited. Arch Dis Child Fetal Neonatal Ed 82(2):F163–F166. https://doi.org/10.1136/fn.82.2.f163
Stone DL, Tayebi N, Orvisky E, Stubblefield B, Madike V, Sidransky E (2000b) Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease. Hum Mutat 15(2):181–188. https://doi.org/10.1002/(SICI)1098-1004(200002)15:2<181::AIDHUMU7>3.0.CO;2-S
Weiss K, Gonzalez A, Lopez G, Pedoeim L, Groden C, Sidransky E (2015) The clinical management of type 2 Gaucher disease. Mol Genet Metab 114(2):110–122. https://doi.org/10.1016/j.ymgme.2014.11.008
Acknowledgements
Details of the contributions of individual authors.
Conception and design of the article: S. Kılavuz, M. Basaranoglu, D. Bako, A. Ozer. Draft of the article: N. Onenli-Mungan, S. Epcacan, YN. Donmez, S. Kılavuz, A. Tukun, N. Onenli-Mungan. Definition of intellectual content: S. Kılavuz, N. Onenli-Mungan, M. Basaranoglu, D. Bako, A. Ozer, H. Geylani Literature search: S. Epcacan, D. Bako, EI Ceylan, M. Basaranoglu. Data acquisition: S. Kılavuz, N. Onenli-Mungan, EI Ceylan. Data analysis: S. Kılavuz, M. Basaranoglu, A. Ozer, S. Ceylaner, A. Tukun. Manuscript preparation: S. Kılavuz, M. Basaranoglu, A. Ozer, D. Bako, N. Onenli-Mungan. Manuscript editing: S. Kılavuz, M. Basaranoglu, EI. Ceylan,YN. Donmez, D.Bako. Manuscript review: S. Kılavuz, N. Onenli Mungan, M. Basaranoglu. Guarantor: S. Kılavuz.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
Ethical committee approval is not required for retrospective clinical studies.
Patient consent statements were obtained from all the legal guardians of the patients. Consent for the use of patient pictures was also obtained.
Informed consent
Additional informed consent was obtained from all participants for whom identifying information was included in this article.
Conflict of interest
There are no conflicts of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
About this article
Cite this article
Kılavuz, S., Basaranoglu, M., Epcacan, S. et al. A rare cause of hydrops fetalis in two Gaucher disease type 2 patients with a novel mutation. Metab Brain Dis 37, 1283–1287 (2022). https://doi.org/10.1007/s11011-022-00942-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-022-00942-5