Recognizing Gaucher disease in the fifth decade and beyond: a retrospective case study in patients of Ashkenazi Jewish descent

Abstract

Gaucher disease (GD) results in visceral, hematological, and skeletal manifestations. The Ashkenazi Jewish (AJ) population has the highest prevalence due to a founder effect involving the glucocerebrosidase-1 (GBA1) p.N409S variant. Despite this high prevalence, diagnosis can be delayed. We present clinical findings from 20 patients of AJ descent diagnosed with GD type 1 (GD1) at ≥ 50 years of age. Sixty percent underwent bone marrow biopsy as part of their clinical work-up; 20% had a positive family history; 15% were diagnosed during Parkinson’s disease evaluation; and one patient was identified incidentally through carrier screening. Presenting signs/symptoms included splenomegaly, osteopenia/osteoporosis, thrombocytopenia, anemia, bone/joint pain, lytic lesions/avascular necrosis/pathological fractures, pulmonary manifestations, and parkinsonism. All patients had elevated plasma glucosylsphingosine (lyso-Gb₁). Our data show disease manifestations in AJ patients diagnosed ≥ 50 years, with 15 of 20 initiating treatment. This work underscores the importance of maintaining a high index of clinical suspicion for GD and highlights the importance of timely disease recognition.

Keywords

Gaucher disease / Ashkenazi Jewish / lyso-Gb₁ / Parkinson’s disease / carrier screening

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