Gaucher's Disease

Diagnosis

Gaucher's Disease

History

A 8-year-old girl was admitted evaluation of massive hepatosplenomegaly. Laboratory findings showed anemia ( Hb = 112; N 115-155 g/L) and thrombocytopenia ( Platelets = 61 ; N 140-440 10^9/L). C Reactive protein was normal at 0.9. A F18-FDG PET/CT  was requested to rule out leukemia/lymphoma.

Findings

Mildly hypermetabolic massive splenomegaly with some degree of hepatomegaly. There is bone marrow expansion without focal bony lesions. The absence of significant lymph nodes activity, focal uptake in the liver, spleen and bone made the diagnosis of malignancy less likely.

Discussion

Bone marrow biopsy  showed spumous histiocytes with some eccentric nuclei.  Assay of lysosomal enzymes  in the leukocytes demonstrated a reduced activity of ß-Glucosidase enzyme: 3.7 nmol/h/mg of protein  (normal control 10.6). Diagnosis was made of Gaucher disease [1,2].

Diverse nuclear medicine procedures have been used to assess Gaucher disease: Tc99-MDP for bone infarcts  and  Tc99m-sulfur colloid for the evaluation of the reticuloendothelial system following enzyme replacement therapy showing reduction of bone marrow expansion and lung uptake [3,4]. Tc99m-MIBI have been shown to  accumulate in the glucosidase laden macrophages, demonstrating a more specific distribution of the disease than Tc99-sulfur colloid [5].  More recently, F18-FDG PET/CT has been  proposed  as an alternative to Tc99m-MIBI to monitor bone marrow disease.   As proposed for Tc99m-Sestamibi, F18-FDG uptake is likely due to direct accumulation in Gaucher cells [6].  Focal infiltration of the spleen by Gaucher has also been reported  with F18-FDG [7] . More recently, direct labelling of ß-Glucosidase with F18 has been performed and studied in a murine model [8]. The exact role of  PET/CT in Gaucher disease remains to be clarified.

References

[1] Linari S, Castaman G. Clinical manifestations and management of Gaucher disease. Clin Cases Miner Bone Metab 2015;12:157-164

[2] Dandana A, Khelifa SB, Chahed H, Miled A, Ferchichi S. Gaucher disease: clinical, biological and therapeutic aspects. Pathobiology 2016;83:13-23

[3] Katz K, Mechlis-Frish S, Cohen J, Horev G, Zaizov R, Lubin E. Bone scans in the diagnosis of bone crisis in patients who have Gaucher disease. J Bone Joint Surg 1991;73-A:513-517

[4] Lorberboym M, Pastores GM, Kim CK, Heman G, Glajchen N, Machac J. Scintigraphic monitoring of reticuloendothelial system in patients with Type 1 Gaucher disease on enzyme replacement therapy. J Nucl Med 1997;38:890-895.

[5] Mariani G, Filocamo M, Giona F, Villa G, Amendola A, Erba P, Buffoni F, Copello F, Pierini A, Minichilli F, Gatti R, Brady RO. Severity of bone marrow involvement in patients with Gaucher's disease evaluated by scintigraphy with Tc99m-Sestamibi.

[6] Mariani G, Erba PA, Perri M, Sollini M, Lazzeri E, Linari S. Assessment of bone marrow disease in Gaucher disease using PET with F18-FDG. Mol Genet Metabolism 2014;111:S74

 [7] Metser U, Even-Sapir E. The role of F18-FDG PET/CT in the evaluation of solid splenic masses.Semin Ultrasound CTMRI 2006;27:420-425

[8] Phenix CP, Rempel BP, Colobong K, Doudet DJ, Adam MJ, Clarke LA,Wither SG. Imaging of enzyme