D2.325 - Desensitization of Olipudase alfa-induced anaphylaxis in a child with chronic neurovisceral acid sphingomyelinase deficiency and ochoa syndrome

Introduction:Olipudase alfa is indicated for the non-central nervous system manifestations of acidsphingomyelinase deficiency (ASMD). Anaphylaxis is a very rare and life-threatening adverse reactiondescribed for this drug. Here, we report the case of a 13-year-old girl affected by chronicneurovisceral ASMD who experienced olipudase alfa proper anaphylactic reaction during the 12thadministration of the target therapeutic dose of 3 mg/kg.

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Case Presentation:A 13-year-old girl admitted to department of metabolism for the first time with cytopenia,hepatosplenomegaly, and upward gaze restriction at the age of 6. She was diagnosed with alysosomal storage disorder by low sphingomyelinase enzyme 1.33 μmol/L/h (Ng>2 μmol/L/h) leveland an SMPD1(c.502G>A (p.G168R) mutation. Enzyme replacement therapy (ERT) for compassionateuse was introduced at the age of 12 years-old, after obtaining informed parental consent .Whilereceiving the 20th dose of olipudase alfa ERT, periorbital edema, widespread urticarial rash on theback, and hypotension developed within one hour. This situation was assessed as anaphylaxis andadrenaline was administered. The treatment was stopped for 2 weeks and then a 12-stepdesensitization protocol with the infused dose of 2 mg/kg (two dose) was applied, successfullyreaching a therapeutic dose of 3 mg/kg.

Conclusion:This report presents the second case in the literature of anaphylaxis to olipudase alfa in a childaffected by chronic neurovisceral acid sphingomyelinase deficiency (ASMD) and describe a 12-stepdesensitization procedure. This procedure, with the total administered dose of 2 mg/kg (two dose) ,followed by gradual dose escalation, allowed to reach the dose of 3 mg/ kg without adversereactions.