Rare GBA1 genotype in two siblings with a severe bone phenotype of type 1 Gaucher disease

• Published in: Molecular genetics and metabolism 2019-02, Vol.126 (2), p.S115-S115
• Main Authors: Paskulin, Livia D., Starosta, Rodrigo T., Zizemer, Vitoria S., Basgalupp, Suelen, Schwartz, Ida Vanessa D.
• Format: Article
• Language: English
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2018.12.293

Introduction: Gaucher disease type 1 (GD1) is a lysosomal storage disorder characterised by a variable phenotype ranging from oligosymptomatic patients to severe visceral and bone manifestations. Herein we present two cases of siblings diagnosed with GD1 with a rare genotype and a particular phenotype. Case report: Patient 1 is a 47 years-old female diagnosed with GD1 when 42 after evaluation for hyperferritinaemia. At first evaluation she had chronic lumbar pain with Bone Marrow Burdeen score = 14 (severe), mild splenomegaly, ferritin = 588.2ng/mL, normal platelets and Hb values, chitotriosidase activity = 9,609nmol/mL/h. Patient started therapy with miglustat (since bone pain was a main feature of her phenotype) but changed to alfa-taliglucerase due to gastrointestinal adverse effects and worsening of hyperferritinaemia due to allergic reaction to alfa-taliglucerase infusion, therapy was changed to imiglucerase (current treatment). Patient 2, the older sister of patient 1, is 50 years old and was diagnosed with GD1 when 45 after an osteonecrosis of the left femur and a total hysterectomy for uncontrollable bleeding. At first evaluation, she had bone pain with a Bone Marrow Burden score = 14 (severe), mild splenomegaly, anaemia (Hb = 11.5 g/dL), normal platelets count, chitotriosidase activity of 2970nmol/mL/h. Patient started treatment with miglustat, and after 48 months changed to alfa-taliglucerase due to bone pain and platelets decrease. Upon genotyping with next-generation sequencing, both patients were discovered to be compound GBA1 heterozygotes for E349K and S366N mutations. Conclusion: To our knowledge, this is the first case presented of the GBA1 genotype E349K/S366N in patients with GD. The case is remarkable in that the bone disease is the most prominent feature in the phenotype, with both patients presenting BMB scores as high as 14, and in that visceral and haematological manifestations are only mild.