Enzyme reconstitution/replacement therapy for lysosomal storage diseases.
OBJECTIVE
Over the past 15 years, the lysosomal storage diseases have become paradigms for the specific treatment of monogenic disorders, particularly those affecting children. This review summarizes the phenotypes and recent literature regarding enzyme reconstitution (replacement) therapy and outcomes for such treatable lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease and the mucopolysaccharidoses.


RESULTS
Recent clinical trials have shown that enzyme reconstitution therapy effectively treats many of the manifestations of the lysosomal storage diseases. When initiated early in the disease course, enzyme reconstitution therapy can reverse some disease manifestations, but may not completely alleviate the disease progression. Enzyme reconstitution therapy is generally well tolerated. Many adverse events are antibody-related, but can be managed without requiring cessation of enzyme reconstitution therapy. Documented IgE reactions, i.e. anaphylactoid, are quite rare (fewer than 1%).


CONCLUSIONS
Enzyme reconstitution therapy is a safe and effective treatment modality available for several of the lysosomal storage diseases. Owing to the short history of enzyme reconstitution therapy, the long-term outcomes of enzyme reconstitution therapy-treated individuals are unknown and require further investigation. Medical professionals must learn to identify patients likely to benefit from these life-changing therapies so as to prevent many of the devastating, irreversible complications of the lysosomal storage diseases.
Burrow
T Andrew
TA
Division of Human Genetics, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
Hopkin
Robert J
RJ
Leslie
Nancy D
ND
Tinkle
Bradley T
BT
Grabowski
Gregory A
GA
D002648:Child; D017281:Cost of Illness; D018450:Disease Progression; D000795:Fabry Disease / Q000188:drug therapy / Q000628:therapy; D005962:Glucosylceramidase / Q000627:therapeutic use; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy; D006801:Humans; D007066:Iduronate Sulfatase / Q000627:therapeutic use; D016464:Lysosomal Storage Diseases / Q000188:drug therapy* / Q000191:economics / Q000235:genetics*; D009083:Mucopolysaccharidoses / Q000628:therapy; D000519:alpha-Galactosidase / Q000627:therapeutic use
C070292:alglucerase; D007066:Iduronate Sulfatase; C517982:idursulfase; D000519:alpha-Galactosidase; D005962:Glucosylceramidase