Unsuspected Gaucher disease in a splenectomized young adult with acute onset of back pain

Mariana Serres Gomez ¹ Dayebgadoh Gerald ² Gisele Pino ² Brendan Lanpher ³ Alma R Oskarsdottir ⁴ Kaaren K Reichard ⁴ Karen L Rech ⁴ Devin Oglesbee ² Dietrich Matern ²

¹Deparment of Laboratory Medicine, La Paz University Hospital, Spain
²Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, USA
³Department of Clinical Genomics, Mayo Clinic, USA
⁴Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, USA

BACKGROUND

Gaucher disease (GD) is an autosomal recessive lysosomal disorder due to β-glucocerebrosidase (GBA) deficiency, which leads to glucocerebroside accumulation in macrophages and formation of Gaucher cells in spleen, liver, and bone marrow. Clinical consequences include hepatosplenomegaly, anemia and/or thrombocytopenia and bone complications.

CASE REPORT

A 13-year-old asymptomatic male was found to have splenomegaly during a routine sport physical. A biopsy revealed a littoral cell angioma, a very rare, usually benign tumor, and he had a splenectomy. At 18 years old he was referred to the Emergency Department for acute onset of bilateral back pain in the setting of a recent viral-like illness.

RESULTS

CT of the abdomen and pelvis showed marked hepatomegaly. MRI of the lumbar spine demonstrated diffuse T1 hypointense marrow of the vertebra, compatible with a myeloproliferative/lymphoproliferative process or lysosomal disorders given the hepatomegaly, bone pain, and history of splenectomy. An additional PET scan demonstrated diffusely increased FDG uptake suspicious for a hematopoietic/lymphoproliferative disease. Flow cytometry showed normal immunophenotyping with no monotypic B-cells. Bone marrow demonstrated extensive medullary coagulative necrosis with residual ghost cells which resembled histocytes (CD163 positive staining). GBA activity was reduced (0.35 nmol/h/mg protein; reference: ≥3.53). Plasma glucopsychosine and molecular genetic testing confirmed GD (glucopsychosine: 0.48 nmol/mL, reference: ≤0.003; compound heterozygosity for two GBA1 variants: c.1226A>G classified as pathogenic, and c.685G>A as of uncertain significance). The patient was referred for genetic counselling and enzyme replacement therapy.

DISCUSSION/CONCLUSION

The clinical presentation was consistent with type 1 or non-neuronopathic GD. This case highlights the importance of including inborn errors of metabolism in the differential diagnosis of suspected hematological conditions.