Clinical utility of different bone marrow examination methods in the diagnosis of adults with sporadic Gaucher disease type 1.
Dear Editor, Gaucher disease (GD) is the most common lysosomal storage disease, characterized by glucosylceramide accumulation in macrophages owing to inherited glucocerebrosidase deficiency caused by GBA1 mutation . Clinical manifestations include thrombocytopenia, hepatosplenomegaly, bone pain, osteopenia, dyspnea, and seizure, depending on the organ involved . Among these, neurologic involvement plays a crucial role in the classification of the following three subtypes: GD types 1, 2, and 3, called non-neuronopathic, acute neuronopathic, and chronic neuronopathic types, respectively [1, 2]. β-glucocerebrosidase activity in peripheral leukocyte is considered the confirmatory diagnostic indicator of GD . Bone marrow (BM) study to detect Gaucher cells (GCs) with the classical “wrinkled tissue paper” appearance has not been routinely recommended because of procedural risks and false-positive results . We present a patient with recurrent seizures as a sole symptom who was correctly diagnosed as having GD type 3 through a BM study. A 31-yr-old woman with recurrent seizures was referred to our hospital. She experienced the first seizure attack at the age of 23 yr. Despite constant antiepileptic medications at the outpatient clinic, she had drug-resistant myoclonic seizures, intermittently evolving to generalized tonic-clonic seizures, which required 11 hospital admissions during the last three years. The initial complete blood count showed no specific findings other than mild leukopenia, with the following values: hemoglobin, 11.9 g/dL; platelets, 162×10/L; and leukocytes, 3.32×10/L, with normal differential counts (Fig. 1A). Physical examination and abdominal ultrasonography revealed no evidence of splenomegaly or hepatomegaly. Drug-induced leukopenia related with long-term use of antiepileptic medications was initially suspected, but the patient showed mild leukopenia during the recent eight weeks, with leukocyte levels ranging from 3.00×10/ L to 3.59 ×10/L. Accordingly, the attending physician performed a BM study. In hypocellular marrow with normal distribution, GCs accounted for 17.5% of all nucleated cells on the aspiration smear (Fig. 1B). Of the GCs, 10.5% showed atypical vacuolations, while the others showed typical fibrillary cytoplasm with an eccentrically placed nucleus (Fig. 1C). Despite the consistent BM biopsy findings of GCs (Fig. 1D), reticulin staining showed no evidence of abnormal reticulin fibrosis (i.e., grade 0). In addition, β-glucocerebrosidase activity test revealed 0.6 nmol/hr/mg protein, which is much lower than the reference limit of 6.0 nmol/hr/mg protein. GBA1 sequencing to confirm the diagnosis revealed two point mutations (i.e., N188S and R257Q), both