CRIM status in Pompe disease

Pompe disease or glycogenosis type II (GSD II) is a LSD resulting from a deficiency of the enzyme acid α-glucosidase (GAA) , and is inherited in an autosomal recessivemode.The gene has been localized to chromosome ۱۷q۲۱-۲۳.The gene has been cloned and contains ۲۰ exons. It is estimated that there are between ۵,۰۰۰ and ۱۰,۰۰۰ peoplearound the world living with Pompe disease. Until recently, the only therapeutic option for Pompe disease was supportive care. Enzyme replacement therapy (ERT) with rhGAA is now available and has the ability to treat the underlying cause of Pompe disease. Although ERT is not a cure, providing the missing enzyme may slow or halt theprogression of muscle weakness and improve muscle function. However there are patients who have not had a good outcome despite early treatment. The long-termefficacy and safety to rhGAA (Myozyme) administration may be affected by many factors, including patient phenotype and genotype, the timing of the initiation oftreatment, and the development of an immune response, which is the most important, potentially modifiable factor. Cross-reactive immunologic material (CRIM) status hasbeen found to be an important predictive factor for immune responses to rhGAA replacement therapy in infantile-onset patients. CRIM negative patients (approximately۲۰% of classical infantile patients) are unable to make any GAA protein, due to the presence of underlying deleterious null GAA alleles, and as a result their immune systemrecognizes rhGAA as a foreign protein and despite being on ERT, these patients usually fare poorly due to development of a sustained high titer of neutralizing antibodies torhGAA that renders the treatment ineffective. In contrast, CRIM-positive patients produce some residual GAA protein, although non-functional inactive form. Theytypically have low antibody titers and a better clinical outcome without the need for immunomodulation. High, sustained antibody titers are also noted in some late onsetPompe patients. The reason for these differing responses can be at CRIM status is determined on Western blot analysis, in skin fibroblasts, but unfortunately CRIM statustesting is not available in our country and can be performed at specialized academic or commercial laboratories.

کلیدواژه ها:

Myozyme ، Pome ، Crime Status.