Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography

Abstract

Background: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. Objectives: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. Methods: Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. Results: By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P =.002), in splenectomized patients (P =.012) and those with dysphagia (P <.001). Liver stiffness was positively correlated with age of onset of ERT (P <.001). PGRN levels were significantly lower in GD patients compared with controls (P <.001). PGRN was significantly lower in GD patients with squint (P =.025), dysphagia (P =.036) and elevated liver stiffness (P =.015). PGRN was positively correlated with white blood cell count (r =.455, P =.002) and haemoglobin (r =.546, P <.001), while negatively correlated with severity score index (r = −.529, P <.001), liver volume (r = −.298, P =.034) and liver stiffness (r = −.652, P <.001). Conclusions: Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.