CRIM-negative infantile Pompe disease: 42-month treatment outcome.

Pompe disease is a rare lysosomal glycogen storage disorder characterized by deficiency of acid α-glucosidase enzyme (GAA) and caused by mutations in the GAA gene. Infantile-type Pompe disease is a multiorgan disorder presenting with cardiomyopathy, hypotonia, and muscular weakness, which is usually fatal. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) has recently been shown to be effective and subsequently yielded promising results in cross-reactive immunologic material (CRIM)-positive patients. CRIM-negative patients showed a limited response to ERT and died or were ventilator dependant. Over a period of 44 months, we monitored cognitive and motor development, behavior, auditory function, and brain imaging of a CRIM-negative infantile Pompe disease patient on rhGAA and monoclonal anti-immunoglobulin E (anti-IgE) antibody (omalizumab) treatment due to severe allergic reaction. Cardiorespiratory and skeletal muscle response was significant, with almost normal motor development. Cognitive development-in particular, speech and language-deviated increasingly from normal age-appropriate development and was markedly delayed at 44 months, unexplained by moderate sensorineural hearing impairment. Brain magnetic resonance imaging (MRI) at 18, 30, and 44 months of age revealed symmetrical signal alteration of the deep white matter. Titer values of IgG antibodies to rhGAA always remained <1:800. The potential role of omalizumab in immune modulation remains to be elucidated; however, this is the first report presenting a ventilator-free survival of a CRIM-negative patient beyond the age of 36 months. The central nervous system (CNS) findings are hypothesized to be part of a yet not fully described CNS phenotype in treated patients with longer survival.

Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children: safety and tolerance.

Background & Objective. Ultrarush induction for specific venom immunotherapy has been shown to be reliable and efficacious in adults. In this study its safety and tolerance in children was evaluated. Methods. Retrospective analysis of 102 ultrarush desensitizations carried out between 1997 and 2005 in 94 children, aged 4 to 15 years. Diagnosis and selection for immunotherapy were according to recommendations of the European Academy of Allergy and Clinical Immunology. Systemic adverse reactions (SARs) were described using the classification of H. L. Mueller. Results. All patients reached the cumulative dose of 111.1 µg hymenoptera venom within 210 minutes. Six patients (6%) had allergic reactions grade I; 2 patients (2%) grade II and 5 patients (5%) grade III. Three patients (3%) showed unclassified reactions. SARs did not occur in the 15 patients aged 4 to 8 years and they were significantly more frequent in girls (29%) compared with boys (12%) (P = 0.034, multivariant analysis) and in bee venom extract treated patients (20%) compared to those treated with wasp venom extract (8%) (OR 0.33, 95% Cl 0.07-1.25). Conclusion. Initiation of specific immunotherapy by ultrarush regimen is safe and well tolerated in children and should be considered for treating children with allergy to hymenoptera venom.