The Practicality of Family screening for Gaucher disease among first- and second-degree relatives: an effective diagnostic approach in high consanguinity

Document Type : Original Article

Authors

1 Genetics of Non-communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan Iran.

2 School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

3 Department of Infectious Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Abstract

Gaucher Disease occurs more frequently in the offspring of familial marriages. With a wide variety of presentations, the long list of tests required to confirm GD in addition to those needed to rule out others puts a heavy financial burden on the patients, especially in regions where the majority live below the poverty line. Thus, in this study, we provide a familial screening method in patients whose relatives are confirmed GD cases, assuming that this approach might ease up the process.
In this study, 26 patients out of 217, whose family members were GD patients and had symptoms associated with GD were selected. Enzyme assay levels using Dried-Blood Samples from 3ml of samples were measured. Those with low levels of enzyme assay were further tested with GBA gene sequencing to confirm the diagnosis. The results of the sequencing revealed 5 carriers and 1 GD patient. Genetic counseling for GD on a personalized level is novel in the region, which all our patients received and responded positively to. In conclusion this process eases the diagnosis and reduces the overall burden of GD while keeping genetic counseling for the patients, which provides better care and opens up the possibilities of a registry system for GD patients and susceptible individuals in low-income countries.

Keywords

Main Subjects

References

Amato D, Stachiw T, Clarke JTR, Rivard GE. Gaucher disease: Variability in phenotype among siblings. Journal of Inherited Metabolic Disease. 2004;27(5):659-69.
Bonesteele G, Gargus JJ, Curtin E, Tang M, Rosenbloom B, Kimonis V. Diffuse large B-cell non-Hodgkin's lymphoma in Gaucher disease. Molecular Genetics and Metabolism Reports. 2020;25:100663.
Chiong MAD, Racoma MJC, Abacan MAR. Genetic and clinical characteristics of Filipino patients with Gaucher disease. Molecular Genetics and Metabolism Reports. 2018;15:110-5.
Davari M, Nabizadeh A, Kadivar M, Asl AA, Sarkheil P. Healthcare resource utilization and cost of care for Gaucher patients in Iran. J Diabetes Metab Disord. 2019;18(1):127-32.
Daykin EC, Ryan E, Sidransky E. Diagnosing neuronopathic Gaucher disease: New considerations and challenges in assigning Gaucher phenotypes. Mol Genet Metab. 2021;132(2):49-58.
Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Molecular Genetics and Metabolism Reports. 2019;18:19-21.
Huang Y, Jia X, Tang C, Liu S, Sheng H, Zhao X, et al. High risk screening for Gaucher disease in patients with splenomegaly and/or thrombocytopenia in China: 55 cases identified. Clin Chim Acta. 2020;506:22-7.
Kang L, Zhan X, Gu X, Zhang H. Successful newborn screening for Gaucher disease using fluorometric assay in China. Journal of Human Genetics. 2017;62(8):763-8.
Kishnani PS, Al-Hertani W, Balwani M, Göker-Alpan Ö, Lau HA, Wasserstein M, et al. Screening, patient identification, evaluation, and treatment in patients with Gaucher disease: Results from a Delphi consensus. Molecular Genetics and Metabolism. 2022;135(2):154-62.
Lei K, Zhao Y, Sun L, Liang H, Luo R, Sun X, et al. A pilot screening of high-risk Gaucher disease children using dried blood spot methods in Shandong province of China. Orphanet J Rare Dis. 2018;13(1):48.
Leonart LP, Tonin F, Silva MR, Szpak R, Lombardi NF, Fachi MM, et al. CO138 Systematic Review and Meta-Analyses of Longitudinal Studies on Drug Treatments for Gaucher Disease: Focus on Hematological Parameters. Value in Health. 2022;25(7):S330-S.
Martínez-Bailén M, Clemente F, Matassini C, Cardona F. GCase Enhancers: A Potential Therapeutic Option for Gaucher Disease and Other Neurological Disorders. Pharmaceuticals (Basel). 2022;15(7).
Mirbagherijam M. The Main Cause of Exchange Rate Increasing (US Dollar) in Iran. SSRN. 2019.
Miri-Moghaddam E, Velayati A, Naderi M, Tayebi N, Sidransky E. Coinheritance of Gaucher disease and α-thalassemia resulting in confusion between two inherited hematologic diseases. Blood Cells Mol Dis. 2011;46(1):88-91.
Miyamoto T, Iino M, Komorizono Y, Kiguchi T, Furukawa N, Otsuka M, et al. Screening for Gaucher Disease Using Dried Blood Spot Tests: A Japanese Multicenter, Cross-sectional Survey. Intern Med. 2021;60(5):699-707.
Momosaki K, Kido J, Matsumoto S, Yoshida S, Takei A, Miyabayashi T, et al. High-risk screening for Gaucher disease in patients with neurological symptoms. Journal of Human Genetics. 2018;63(6):717-21.
Nabizadeh A, Davari M, Kadivar M, abddollahi Asl A. PSY97 - COST-EFFECTIVENESS ANALYSIS OF ENZYME REPLACEMENT THERAPY FOR TYPE 1 GAUCHER DISEASE. Value in Health. 2018;21:S452-S.
Ortiz-Cabrera NV, Gallego-Merlo J, Vélez-Monsalve C, de Nicolas R, Mas SF, Ayuso C, et al. Nine-year experience in Gaucher disease diagnosis at the Spanish reference center Fundación Jiménez Díaz. Molecular Genetics and Metabolism Reports. 2016;9:79-85.
Pastores GM, Hughes DA. Gaucher Disease. GeneReviews. 2018.
Qi X, Xu J, Shan L, Li Y, Cui Y, Liu H, et al. Economic burden and health related quality of life of ultra-rare Gaucher disease in China. Orphanet Journal of Rare Diseases. 2021;16(1):358.
Roh J, Subramanian S, Weinreb NJ, Kartha RV. Gaucher disease – more than just a rare lipid storage disease. Journal of Molecular Medicine. 2022;100(4):499-518.
Rosenblum LS, Zhu H, Zhou Z, Teicher J, Heim RA, Leach NT. Comparison of pan-ethnic and ethnic-based carrier screening panels for individuals of Ashkenazi Jewish descent. Journal of Genetic Counseling. 2020;29(1):56-66.
Saadat M, Zarghami M. Consanguineous Marriages Among Iranian Mandaeans Living in South-West Iran. J Biosoc Sci. 2018;50(4):451-6.
Sajadi HS, Ehsani-Chimeh E, Majdzadeh R. Universal health coverage in Iran: Where we stand and how we can move forward. Med J Islam Repub Iran. 2019;33:9.
Sawada T, Kido J, Sugawara K, Yoshida S, Matsumoto S, Shimazu T, et al. Newborn screening for Gaucher disease in Japan. Molecular Genetics and Metabolism Reports. 2022;31:100850.
Sestito S, Filocamo M, Ceravolo F, Falvo F, Grisolia M, Moricca MT, et al. Norrbottnian clinical variant of Gaucher disease in Southern Italy. Journal of Human Genetics. 2017;62(4):507-11.
Somaraju UR, Tadepalli K. Hematopoietic stem cell transplantation for Gaucher disease. Cochrane Database Syst Rev. 2017;10(10):Cd006974.
Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, et al. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017;18(2):441.
Stirnemann J, Vigan M, Hamroun D, Heraoui D, Rossi-Semerano L, Berger MG, et al. The French Gaucher’s disease registry: clinical characteristics, complications and treatment of 562 patients. Orphanet Journal of Rare Diseases. 2012;7(1):77.
Sun XY, Xue Y, Wang YP, Huang J, Lin RF, Kang MY, et al. [Clinical phenotype and genotype of Gaucher disease in 14 children]. Zhonghua Er Ke Za Zhi. 2022;60(6):527-32.
van Dussen L, Biegstraaten M, Hollak CE, Dijkgraaf MG. Cost-effectiveness of enzyme replacement therapy for type 1 Gaucher disease. Orphanet J Rare Dis. 2014;9:51.
Van Rossum A, Holsopple M. Enzyme Replacement or Substrate Reduction? A Review of Gaucher Disease Treatment Options. Hosp Pharm. 2016;51(7):553-63.
Weinreb NJ, Goker-Alpan O, Kishnani PS, Longo N, Burrow TA, Bernat JA, et al. The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here? Mol Genet Metab. 2022;136(1):4-21.
Zuckerman S, Lahad A, Shmueli A, Zimran A, Peleg L, Orr-Urtreger A, et al. Carrier Screening for Gaucher DiseaseLessons for Low-Penetrance, Treatable Diseases. JAMA. 2007;298(11):1281-90.
Journal of Epigenetics
Volume 4, Issue 1 - Serial Number 1
September 2023
Pages 23-15

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History

  • Receive Date: 29 January 2023
  • Revise Date: 15 August 2023
  • Accept Date: 03 September 2023

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