Cessation of enzyme replacement therapy in Gaucher disease.
OBJECTIVE
Enzyme replacement therapy (ERT) is a promising therapeutic intervention for lysosomal storage diseases. Posttranslationally engineered human beta-glucocerebrosidase (Ceredase/Cerezyme) is commercially available and is the standard ERT for Type I Gaucher disease. Cessation of therapy is sometimes necessary for personal or financial reasons, but the consequences of discontinuation are unknown. This study reports results of discontinuing therapy in four patients with Type I Gaucher disease with different genotypes and varying degrees of clinical involvement.


METHODS
Patient genotypes were as follows: N370S/L444P (Patients 1 and 2), K79N/K79N (Patient 3), and N370S/N370S (Patient 4). All were evaluated before, during, and after withdrawal from ERT. Patients 1, 2, and 3 were studied after reinstituting ERT. The following parameters were documented at 3- to 12-month intervals in all patients: hemoglobin, platelet count, angiotensin-converting enzyme, spleen volume, liver volume, femoral magnetic resonance imaging, bone density, and urinary pyridinium crosslinks.


RESULTS
After cessation of therapy, Patients 1, 2, and 3 had more dramatic regression in hematological and visceral parameters than Patient 4 and required reinstitution of ERT within 2 years. All three patients recovered posttreatment status within 4 years of reinstituting ERT. Patient 4 remained stable 6 years after cessation of ERT.


CONCLUSIONS
Regression of disease status in patients with Type I Gaucher disease after cessation of ERT conformed to the genotype-phenotype relationships of disease onset. Careful monitoring and reinstitution of ERT enabled previously attained treatment status.
Grinzaid
Karen A
KA
Department of Pediatrics, Division of Medical Genetics, Emory University, Atlanta, Georgia 30322, USA.
Geller
Eleanor
E
Hanna
Soheil L
SL
Elsas
Louis J
LJ
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005838:Genotype; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D028761:Withholding Treatment
D011994:Recombinant Proteins; D005962:Glucosylceramidase