Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications

Unusual manifestations and unusual mimics of adult onset Still’s disease

“…Adwan and Dr. Bakri have provided some interesting supplemental information, which is not emphasized much in the literature. The presence of lymphadenopathy in AOSD prompts the inclusion of malignancy in differential diagnosis; however, less attention is given to similar pathologies including Schnitzler syndrome or Gaucher’s disease in clinical practice, both of which are also associated with lymphadenopathy 8,9,10. Our case report is distinct due to the presence of dermatopathic lymphadenopathy, which is not reported in Schnitzler or Gaucher’s disease 1.…”

Iron storage in liver, bone marrow and splenic Gaucheroma reflects residual disease in type 1 Gaucher disease patients on treatment

“…Indeed, it has previously been reported by Boven et al () that different types of macrophages, i.e., the more pro‐inflammatory, classically activated type M1 and anti‐inflammatory, alternatively activated type M2, are present in Gaucher spleen. As these subtypes express different profiles of genes involved in iron storage (Recalcati et al , ) it is possible that the balance in M1‐type and M2‐type macrophages in GD determines the individual pattern of iron storage, as recently reviewed (Regenboog et al , ). In brief, initially, in untreated, early diagnosed GD, an abundance of macrophages with an M1‐signature is present which results in low‐grade inflammation and a trigger for macrophage iron trapping as is described in other pro‐inflammatory states (Ganz & Nemeth, ).…”

“…In GD, the development of malignancies is a main cause of mortality (de Fost et al, 2006;Arends et al, 2013;Weinreb & Lee, 2013). Abnormal metabolism with residual toxic stores of iron might contribute to the increased risk of malignancies (Regenboog et al, 2016a).…”

“…The sequestration of iron in macrophages is probably similar to the mechanism described for anaemia of inflammation (Ganz & Nemeth, ; Nemeth & Ganz, ). It is hypothesized that persistent hyperferritinaemia after years of intensive therapy represents abnormal iron metabolism as well as the presence of residual disease (Lorenz et al , ; Regenboog et al , ). Therefore, iron imaging can possibly aid to locate sites of residual disease which may be related to complication risk.…”

Biomarker combination is necessary for the assessment of Gaucher disease?

“…Glucosylceramide accumulation in macrophages induces an inflammatory response that produces deregulation in iron recycling and cytokine release. Data collected in the Spanish Registry of GD revealed that up to 60% of patients with GD1 have hyperferritinemia (23), which has been associated by some authors with the severity of this disease (24). Hyperferritinemia reverts with ERT with no relationship stablished between this and the mutations in the hemochromatosis gene.…”