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4CPS-031 Efficacy and safety of high-dose twice-weekly sebelipase alfa in severe-onset Wolman disease: a case report
  1. A Castro Balado1,
  2. MJ de Castro López2,
  3. P Sánchez Pintos2,
  4. EJ Bandín Vilar1,
  5. JM Giráldez Montero1,
  6. L García Quintanilla1,
  7. ML Couce Pico2,
  8. I Zarra Ferro1
  1. 1Complejo Hospitalario Universitario de Santiago de Compostela, Hospital Pharmacist Service, Santiago de Compostela, Spain
  2. 2Complejo Hospitalario Universitario de Santiago de Compostela, Paediatric Inherited Metabolic Diseases, Santiago de Compostela, Spain


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

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