VARIABILITY IN MANIFESTATION OF GAUCHER DISEASE SYMPTOMS AND THAT OF A RESPONSE TO ENZYME REPLACEMENT THERAPY BASED ON CLINICAL CASES OF CLOSELY RELATED PATIENTS

The study aims to specify the variability in manifestation of Gaucher disease clinical symptoms and that of a response to enzyme replacement therapy based on clinical cases of closely related patients. Materials and methods. Hematological, gastroenterological, neurological and orthopedic manifestations of Gaucher disease were compared in two patients: a male patient (diagnosed at 9 years old), and a female patient (diagnosed at 21 years old), being close relatives (a whole blood brother and a sister). Results. At diagnosis, both the adult female patient and the child had hepatosplenomegaly with splenomegaly predominating. Both patients had changes in the musculoskeletal system. In addition to the above, the boy had shortening of limbs as well as deformity of chest and abdomen unlike the adult patient, who had femurs deformity of Erlenmeyer flask type. At diagnosis, hematological changes were more severe in the child patient. The obtained data indicate that there is a significant variability in manifestation of symptoms of Gaucher disease. The fact that there is hepatosplenomegaly, thrombocytopenia and a number of orthopedic changes in a patient should become a valid reason to suspect an orphan disease and to carry out further diagnostic tests for Gaucher disease.

1. Luzio J. P., Pryor P. R., Bright N. A. Lysosomes: Fusion and Function // Nat Rev Mol Cell Biol. 2007. Vol. 8, Is. 8. P. 622–632.

2. Solomon M., Muro S. Lysosomal Enzyme Replacement Therapies: Historical Development, Clinical Outcomes, and Future Perspectives // Ad Drug Deliv Rev. 2017. Vol. 118. P. 109–134.

3. Futerman A. H., van Meer G. The Cell Biology of Lysosomal Storage Disorders // Nat Rev Mol Cell Biol. 2004. Vol. 5, Is. 7. P. 554–565.

4. Dardis A., Buratti E. Impact, Characterization, and Rescue of Pre-mRNA Splicing Mutations in Lysosomal Storage Disorders // Genes (Basel). 2018. Vol. 9, Is. 2. P. 73.

5. Pastores G. M., Hughes D. A. Non-Neuronopathic Lysosomal Storage Disorders: Disease Spectrum and Treatments // Best Pract Res Clin Endocrinol Metab. 2015. Vol. 29, Is. 2. P. 173–182.

6. Hoffmann B., Mayatepek E. Neurological Manifestations in Lysosomal Storage Disorders – From Pathology to First Therapeutic Possibilities // Neuropediatrics. 2005. Vol. 36, Is. 5. P. 285–289.

7. Лукина Е. А. Болезнь Гоше: современная диагностика и лечение // Клиническая онкогематология. 2009. № 2. C. 196–199. URL: https://cyberleninka.ru/article/n/bolezn-goshe-sovremennaya-diagnostika-i-lechenie (дата обращения: 20.12.2021).

8. Stirnemann J., Vigan M., Hamroun D. et al. The French Gaucher’s Disease Registry: Clinical Characteristics, Complications and Treatment of 562 Patients // Orphanet J Rare Dis. 2012. Vol. 7. P. 77.

9. Regenboog M., Bohte A. E., Somers I. et al. Imaging Characteristics of Focal Splenic and Hepatic Lesions in Type 1 Gaucher Disease // Blood Cell Mol Dis. 2016. Vol. 60. P. 49–57.

10. Rosenbaum H. Hemorrhagic Aspects of Gaucher Disease // Rambam Maimonides Med J. 2014. Vol. 5, Is. 4. P. e0039. DOI 10.5041/ RMMJ.10173.

11. Aldenhoven M., Sakkers R. J., Boelens J., de Koning T. J., Wulffraat N. M. Musculoskeletal Manifestations of Lysosomal Storage Disorders // Ann Rheum Dis. 2009. Vol. 68, Is. 11. P. 1659–1665. DOI 10.1136/ard.2008.095315.

12. Tylki-Szymańska A., Vellodi A., El-Beshlawy A., Cole J. A., Kolodny E. Neuronopathic Gaucher Disease: Demographic and Clinical Features of 131 Patients Enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry // J Inherit Metab Dis. 2010. Vol. 33, Is. 4. P. 339–346. DOI 10.1007/s10545-009-9009-6.

13. Hruska K. S., LaMarca M. E., Scott C. R., Sidransky E. Gaucher Disease: Mutation and Polymorphism Spectrum in the Glucocerebrosidase Gene (GBA) // Hum Mutat. 2008. Vol. 29, Is. 5. P. 567–583.

14. Weinreb N. J., Charrow J., Andersson H. C. et al. Effectiveness of Enzyme Replacement Therapy in 1028 Patients with Type 1 Gaucher Disease after 2 to 5 Years of Treatment: A Report from the Gaucher Registry // Am J Med. 2002. Vol. 113, Is. 2. P. 112–119.

15. Morris J. L. Velaglucerase Alfa for the Management of Type 1 Gaucher Disease // Clin Ther. 2012. Vol. 34, Is. 2. P. 259–271. DOI 10.1016/j.clinthera.2011.12.017.