Persistence of high sustained antibodies to enzyme replacement therapy despite extensive immunomodulatory therapy in an infant with Pompe disease: need for agents to target antibody-secreting plasma cells.

With the advent of enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA, Myozyme®) for Pompe disease, the clinical course of the disease has changed. We have previously described the poor outcome in cross reactive immunologic material (CRIM)-negative and high-titer CRIM-positive (HTCP) patients secondary to high sustained antibody titers (HSAT) which effectively neutralize ERT efficacy. Various immunomodulation strategies are being explored to diminish the immune response to ERT.

Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience.

Enzyme replacement therapy (ERT) for Pompe disease using recombinant acid alpha-glucosidase (rhGAA) has resulted in increased survival although the clinical response is variable. Cross-reactive immunological material (CRIM)-negative status has been recognized as a poor prognostic factor. CRIM-negative patients make no GAA protein and develop sustained high antibody titers to ERT that render the treatment ineffective.

An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions.

Purpose: Pompe disease (PD) is a progressive metabolic myopathy for which the only available treatment is alglucosidase alfa (Myozyme®). Enzyme replacement therapy (ERT) has improved ventilator-free survival, and cardiac and motor functions in patients with infantile PD. However, for an adequate response to occur, a large amount of enzymes must be infused.

Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment.

Cardiac arrhythmias following anesthesia induction in infantile-onset Pompe disease: a case series.

Background: Patients with infantile-onset Pompe disease suffer from marked hypertrophic cardiomyopathy and an increased risk of arrhythmia. A noncompliant left ventricle predisposes these infants to diastolic heart failure with elevated left ventricular enddiastolic pressure (LVEDP); these patients also commonly develop systolic heart failure. Given this baseline cardiac physiology, coronary perfusion pressure becomes highly sensitive to abrupt changes in diastolic blood pressure (DBP).

Fractures in children with Pompe disease: a potential long-term complication.

Background: Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Classic infantile-onset disease, characterized by cardiomegaly and profound weakness, leads to death in the first year of life from cardiorespiratory failure. Reversal of cardiomyopathy and improved motor function have been shown in clinical trials of rhGAA enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme), recently approved for clinical use.

T locus shows no evidence for linkage disequilibrium or mutation in American Caucasian neural tube defect families.

We investigated the T locus as a candidate gene in a series of patients and families with lumbosacral myelomeningocele. Single-strand conformation polymorphism (SSCP) analysis was used to identify sequence variation in all 8 exons and in intron 7 of this locus. We found evidence of substantial polymorphism within this locus, as previously reported [Papapetrou et al.