RESUMO
Classic infantile Pompe disease (IPD) is a rare lysosomal storage disorder characterized by severe hypertrophic cardiomyopathy and profound muscle weakness. Without treatment, death occurs within the first 2 years of life. Although enzyme replacement therapy (ERT) with alglucosidase alfa has improved survival, treatment outcome is not good in many cases and is largely dependent on age at initiation. The objective of the study was (a) to analyse the different stages in the diagnosis and specific treatment initiation procedure in IPD patients, and (b) to compare clinical and biochemical outcomes depending on age at ERT initiation (<1 month of age vs. <3 months of age). Here, we show satisfactory clinical and biochemical outcomes in two IPD patients after early treatment initiation before 3 months of life with immunomodulatory therapy in the ERT-naïve setting, with a high ERT dose from the beginning. Despite the overall good evolution, the patient who initiated treatment <1 month of life presented even better outcomes than the patient who started treatment <3 months of life, with an earlier normalization of hypertrophic cardiomyopathy, along with CK normalization, highlighting the importance of early treatment initiation in this progressive disease before irreversible muscle damage has occurred.
RESUMO
BACKGROUND: The prevalence of pneumonia in infants with high fever without source (FWS; temperature, > or =39.0 degrees C) and a white blood cell (WBC) count greater than 20 x 10(9)/L (occult pneumonia) has been reported to be 20% before the introduction of the 7-valent pneumococcal conjugated vaccine (PCV7). This is the main reason for carrying out chest x-ray (CXR) on infants with high FWS. The aims of this study were to establish the prevalence of occult pneumonia in well-appearing infants with high FWS (temperature, > or =39.0 degrees C) and a WBC count greater than 20 x 10(9)/L in the era of PCV7 and to analyze the value of WBC, absolute neutrophil count (ANC), and C-reactive protein (CRP) level as predictors of the risk of occult pneumonia in these patients. PATIENTS AND METHODS: We conducted a multicenter prospective study in 4 pediatric emergency departments including children younger than 36 months with FWS (temperature, > or =39.0 degrees C) and a WBC count higher than 20 x 10(9)/L on whom a CXR was performed in the absence of respiratory findings. Physicians completed a questionnaire when observing the infant, and the attending physician or, when in doubt, the radiologist interpreted the CXR. Multivariable binary logistic regression was used to estimate the adjusted relative influences of the aforementioned factors on the prevalence of radiological pneumonia. RESULTS: During an entire year (September 2006 to September 2007), we included 188 infants (aged 1-36 months; 56.2% were males) with high FWS and a WBC count greater than 20 x 10(9)/L (range, 20-44.7 x 10(9)/L) on whom a CXR was performed. Of the 188 chest radiographs obtained, 37 (19.7%) were interpreted by the radiologist. Consolidation in the chest radiographs was detected in 25 (13.3%). The probability of an infant with high FWS and WBC of 20 x 10(9)/L or greater having pneumonia was related to 3 of the studied variables: age, ANC, and serum CRP level. The incidence of pneumonia increased with age (odds ratio [OR] of 2.62 for infants >12 months; 95% confidence interval [95% CI], 1.04-6.60), CRP level greater than 100 mg/L (OR, 3.18; 95% CI, 1.19-8.51), and ANC greater than 20 x 10(9)/L (OR, 3.52; 95% CI, 1.37-9.06). White blood cell count was not predictive of occult pneumonia when ANC was taken into account. CONCLUSIONS: In the era of PCV7, the incidence of pneumonia in infants younger than 36 months with high FWS and WBC count greater than 20 x 10(9)/L seems to be lower than that previously reported. However, this is not a uniform group because the incidence of pneumonia increases in infants older than 12 months and with higher ANC and serum CRP level.
