Background and importance Lysosomal acid lipase (LAL) deficiency is a rare metabolic disease (0.2:10 000) characterised by lysosomal accumulation of cholesterol esters and triglycerides, with a severe and rapidly progressive form known as Wolman disease (WD), usually fatal in the first 6–12 months of life. Sebelipase alfa (SA) is a recombinant human LAL authorised as enzyme replacement. According to the technical data sheet, it is administered weekly and should be started at low doses (1 mg/kg) with a gradual increase according to response, thus avoiding serious hypersensitivity reactions. Dosing twice-weekly with rapid dose escalation had not been previously described in the literature.
Aim and objectives To describe the efficacy and safety of high-dose SA administered twice-weekly in severe WD.
Material and methods We describe the case of a 3-month-old baby diagnosed with WD with secondary haemophagocytic syndrome, admitted to the paediatric critical care unit. Since admission, she presented anaemia, thrombopenia, hyperferritininaemia, altered liver function tests and lipid profile, and massive hepatosplenomegaly. Given the rapid deterioration and critical situation, with severe respiratory and kidney failure, treatment with SA was started at high doses twice-weekly.
Results To date, the patient received 11 doses of SA over 35 days. The first dose was administered at 3 mg/kg, and the subsequent doses at 5 mg/kg, twice-weekly as an intravenous infusion over 240 min. She required mechanical ventilation and continuous haemodialysis for 2.5 weeks; and red blood cell and platelet transfusions repeatedly up to day +24 after the start of SA. Initially, ferritin was 9438 ng/mL, decreasing to 1583 ng/mL at day +35. Transaminases reached a peak (AST: 3×ULN, ALT: 2×ULN) at day +10, being within normal values at day +21, with a slight subsequent elevation without clinical relevance. Bilirubin also reached a peak of 14.7 mg/dL at day +10, being at 6.3 mg/dL at day +35. Lipid profile has not yet reached normal values. A reduction in hepatosplenomegaly was noticeable after 1 month. No adverse effects were reported.
Conclusion and relevance After the diagnosis of WD with aggressive and severe presentation, treatment with high-dose twice-weekly SA has been an effective and well-tolerated treatment so far in our case, although it will be necessary to maintain enzyme replacement for life.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.