Real-World Clinical Experience of Unexpected Thrombocytopenia in Patients with Gaucher Disease as an Initial Diagnostic Clue

Objective: Gaucher disease (GD) is a rare, autosomal recessive genetic disorder, caused by the deficiency of the lysosomal enzyme, glucocerebrosidase. However, diagnosing GD is challenging and frequently delayed owing to its heterogeneous severity and early features. Moreover, it can present at any age from infancy to adulthood. Herein, we present five patients to highlight thrombocytopenia detected incidentally can be an important diagnostic clue for diagnosing GD.

Case 1. An asymptomatic, 35-year-old man with no significant family or medical history was found to have thrombocytopenia (97x109/L) during a routine health check-up. He was referred to the Department of Haematology, and diagnosed with Type 1 GD by bone marrow biopsy and low levels of glucocerebrosidase activity.

Case 2. A 44-year-old woman was referred to the hospital for breast cancer surgery. Thrombocytopenia (81x109/L) was detected during pre-surgical preparation, and she was identified as type 1 GD after undergoing a bone marrow biopsy. She continued to take ERT for GD and was diagnosed with GBA-associated Parkinson’s disease three years ago.

Case 3. A girl was delivered with a collodion membrane all over the body and contractures of the elbows and knees. Borderline splenomegaly and thrombocytopenia (78 x109/L) were noted. On day 2 of life, she developed recurrent central apnea and was diagnosed as Type 2 GD according to pathogenic variants in the GBA gene by NGS and very low levels of glucocerebrosidase activity (0.2 µmol/h/L).

Cases 4 and 5. Two brothers were referred to neurology due to drug-resistant generalised tonic-conic seizures and myoclonus that started at the ages of 16 and 18 years, respectively. Mild thrombocytopenia (80 and 63 x109/L) presented from the onset of epilepsy, but it was thought to be a side effect of valproic acid and was continuously monitored. Whole-exome sequencing was performed to investigate the genetic cause of epilepsy, unexpectedly, two pathogenic variants of GBA were identified (c.680Ag (p.Asn227Ser)//c.689TG (p.Val230Gly), and the activities of β-glucosidase decreased in both patients.

Conclusion: GD should be considered if patients present with isolated thrombocytopenia or thrombocytopenia with various symptoms that can be associated with GD.