PF502 A PROPOSAL OF AN ALGORITHM FOR THE DIAGNOSIS OF TYPE 1 GAUCHER DISEASE STARTING FROM HYPERFERRITINEMIA IN ADULTS

Background: Type 1 Gaucher disease (GD) is a pleiotropic disease due to biallelic mutations in GBA gene, causing a reduction or absence of the activity of beta‐glucocerebrosidase and accumulation of glucocerebroside in macrophages of several organs, mainly in the spleen, liver and bone marrow. A high degree of suspicion based on “high risk clinical patterns” is required for the diagnosis. Splenomegaly, low platelets and anemia are major clues to suspect GD. However recent studies have shown that, particularly when classical features of GD are mild, only a minority of physicians considers GD in the differential diagnosis. Hyperferritinemia is another biochemical abnormality frequently found in GD, and an increasing reason for consultation in Internal Medicine or Hematology. Aims: To improve clinical sensitivity for the suspicion of Gaucher Disease, starting from “unexplained hyperferritinemia” in adults. Methods: We created an algorithm for the differential diagnosis of hyperferritinemia based on clinical evaluation and widely available first level tests (who to screen for Gaucher disease). We applied this algorithm to patients referred to our EuroBloodNet tertiary center for Iron Metabolism for “unexplained hyperferritinemia”. Results: In the last year we diagnosed 2 cases of type 1 GD in adults, in which “unexplained” hyperferritinemia was the clue that led to the right interpretation of the clinical picture and guided diagnosis. Patient 1 was a 60 years old men referred because of persistent hyperferritinemia (near 1,000 mg/l) and normal TSAT (35%) with provisional diagnosis of “non‐HFE Hemochromatosis”. History revealed mild anemia (Hb 12.7 g/dl) and thrombocytopenia (127,000/mmc), which had undergone unnoticed, mild splenomegaly (diameter at US: 12.7 cm). He was assuming L‐Dopa because of a 2‐years history of mild “parkinsonism”. Patient 2 was a 23 years old female referred for “unexplained hyperferritinemia (600 mg/l). History revealed persistent and fluctuant thrombocytopenia (118,000/mmc at our observation) previously attributed to immune thrombocytopenic purpura (ITP), but unresponsive to steroids. Physical examination revealed a mild splenomegaly. Both patients underwent extensive diagnostic evaluation, and were eventually found homozygous for the classical N370S mutation on GBA . Summary/Conclusion: Type 1 GD has to be considered in the differential diagnosis of unexplained hyperferritinemia. Given its marked clinical heterogeneity in adults, certain clues are often under‐estimated, especially when they are mild. We propose a diagnostic algorithm that should help its recognition by centers specialized in iron metabolism, when patients are referred for “unexplained hyperferritinemia”.