Enzyme Replacement Therapy in a Patient with Gaucher Disease Type III: A Paradigmatic Case Showing Severe Adverse Reactions Started a Long Time After the Beginning of Treatment

Abstract

Introduction: There are three recombinant enzymes available for the treatment of Gaucher disease (GD): imiglucerase, velaglucerase alfa, and taliglucerase alfa.Case report: A male GD type III patient, 14 years old, genotype p.L444P/L444, diagnosed at 2 years old. He had been treated with imiglucerase for 9 years since the diagnosis. In 2008, however, he presented a severe adverse reaction to imiglucerase, characterized by cough, laryngeal stridor, and periorbital edema. The infusions were suspended for 3 months when imiglucerase was restarted with premedication and a slower infusion rate. After 5 months, he presented a new adverse reaction with vomiting, tachypnea, cough, and periorbital edema. Intradermal testing confirmed IgE-mediated reaction but serological tests were negative. After 2 years and 10 months with no specific treatment and a significant worsening of the clinical picture, taliglucerase alfa was prescribed, with premedication and a slower infusion rate. At the first infusion, he presented moderate adverse reaction and the infusions were suspended. After 2 months, velaglucerase alfa was initiated uneventfully. He maintains day-hospital infusions without premedication and shows improvement of clinical and laboratory parameters.Conclusion: This is the first report of the use of velaglucerase alfa in patients with GD type III. The use of recombinant enzymes is safe for the majority of GD patients, but severe reactions may occur even many years after the beginning of the treatment. Premedication and slower infusion rate reduce the incidence of adverse reactions but may not solve the problem. This case report further demonstrates the different safety profile among all the recombinant enzymes available for the treatment of GD.

Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long‐term data from phase III clinical trials

“…During the course of study participation, the patient developed neurologic symptoms that are suggestive of type 3 GD, and his GBA genotype, F213I/F213I, is also consistent with type 3 GD [ 26 ]. Velaglucerase alfa is under investigation for type 3 GD ( http://ClinicalTrials.gov identifier NCT01685216), but published clinical data in patients with type 3 GD are so far limited to a single case report [ 27 ].…”

Assessment of Basal Metabolic Rate and Nutritional Status in Patients with Gaucher Disease Type III

“…Clinical, laboratory, and imaging findings were indicative of a more severe disease phenotype in patients 1 and 2 as compared to patient 3; this was corroborated by neurological examination. At the time of inclusion, patient 1 was untreated due to the development of allergic reactions to imiglucerase (Genzyme Corp., Allston, MA) after 10 years of enzyme replacement therapy (ERT) and taliglucerase alfa (Protalix, Carmiel, Israel) as well (Vairo et al 2013). Patient 2 was on imiglucerase ERT (60 IU/kg/infusion), as was patient 3 (60 IU/kg/infusion until age 16 and 30 IU/kg/infusion thereafter).…”

“…Patient 1 had a height-for-age z score of À4.11. At initial assessment, patient 1 had Patient discontinued enzyme replacement therapy after 10 years of treatment due to a severe allergic reaction (Vairo et al 2013) c At the time of assessment, the patient had been off ERT for (1) BMI-for-age and height-for-age z scores of À1.16 and À2.54, respectively, versus À1.09 and À4.27, respectively, at the second assessment. Patient 2 had BMI-for-age and height-for-age z scores of À1.39 and À3.02, respectively, and patient 3 had a BMI of 24.7 kg/m 2 (height-for-age z score at age 19 years: À1.93).…”

Lysosomal Leukodystrophies Lysosomal Storage Diseases Associated With White Matter Abnormalities

“…Another therapeutic modality is substrate reduction therapy, based on small molecule agents that are able to reduce the biosynthesis of the accumulated substrate of the deficient enzyme. 85 The N -butyldeoxynojirimycin, miglustat (Zavesca), was approved as an alternative oral treatment for Gaucher disease with resultant improvement in several clinical endpoints. 86 However, the significant gastrointestinal symptoms (diarrhea), tremors, signs of peripheral neuronopathy, and weight loss observed in treated patients has limited its use.…”