Background Carcinoembryonic antigen–related cell adhesion molecule 5 (CEACAM5/CEA) is a glycosylphosphatidylinositol (GPI)–anchored protein used as a serum tumor marker. Because GPI-anchored proteins may be released into blood in inherited GPI deficiencies (IGDs), we assessed whether serum CEA is a biomarker to support the diagnosis of IGDs. Methods Serum CEA concentrations were measured in patients with IGDs and compared with controls. To examine release mechanisms, GPI-anchor–biosynthesis–deficient cells were transfected with CEACAM5 and CEA in conditioned media was quantified. Secreted fragments were analyzed by mass spectrometry to determine cleavage sites. Results Serum CEA concentrations were significantly elevated in patients with IGDs compared with controls. Following CEACAM5 transfection, cells lacking several GPI-pathway genes secreted large amounts of CEA. Mass spectrometric analysis identified multiple cleavage sites in the secreted CEA fragments, including four corresponding to the ω-sites for GPI anchoring and additional sites consistent with protease-mediated cleavage. Conclusions CEA is expressed on the apical surface of epithelial cells of intestine, stomach, and bronchus, and under normal conditions it does not enter the bloodstream even if released from the cell surface. Therefore, CEA levels are typically low in healthy children, reducing the likelihood of false-positive results compared with alkaline phosphatase. Elevated CEA was observed across most IGD subtypes. In combination with reduced granulocyte CD16 expression, serum CEA may serve as a complementary and robust biomarker for detecting inherited GPI deficiencies and may facilitate screening strategies.
Background Glycosaminoglycans in urine (U-GAG) are diagnostic biomarkers of mucopolysaccharidoses (MPS). How renal dysfunction influences U-GAG/creatinine (crn) ratio in children with chronic kidney disease (CKD) has been scarcely studied. We investigated the influence of glomerular filtration rate (GFR) on U-GAG/crn ratio, and assessed the effect of age, sex, and urine dipstick markers indicating kidney disease (protein, blood, glucose and leukocytes). Methods We examined 96 children (age range 0.25–17.5 years) with CKD. GFR was measured by iohexol clearance using seven time-point blood samples (range GFR 6.3–153 mL/min/1.73m2). U-GAG was measured by a dimethyl-methylene blue (DMB) assay. The reference cohort was samples from the laboratory production from 2017 to 2022 (n = 10,165). Age-adjustment of U-GAG/crn ratio was done after appropriate transformation and regression analysis. The influence of GFR, total urine protein-to-crn ratio (U-PCR), age, sex, and urine dipstick markers on U-GAG/crn ratio were examined through z-scores. Results With correction for U-PCR, GFR correlated positively with U-GAG/crn ratio (p < 0.001), with an effect size of relevance for diagnostic interpretation. Urine blood and glucose was associated with elevated U-GAG/crn ratios, and the U-GAG/crn ratio showed a statistically significant age–sex interaction at the onset of puberty (p < 0.001). Conclusion GFR, U-PCR, age and sex are significant covariates of U-GAG/crn ratio and should be assessed if U-GAG/crn ratio does not fit the clinical picture. Reduced GFR may be associated with an increased risk of false negative MPS screening, while increased U-PCR may be associated with false positive MPS screenings. Synopsis GFR influences glycosaminoglycans in urine.
Background Enzyme replacement therapy (ERT) is the cornerstone of disease-specific treatment in late-onset Pompe disease (LOPD), but long-term treatment may be complicated by infusion-associated reactions (IARs), including hypersensitivity reactions and anaphylaxis. Practical management, including rechallenge, desensitization, and indications for immunologic or allergologic evaluation, remains insufficiently standardized. Methods We performed a systematic review in accordance with PRISMA 2020. PubMed/MEDLINE and Cochrane/CENTRAL were searched on 28 September 2026 for reports on IARs or hypersensitivity reactions during ERT in LOPD. Eligible reports included clinical trials, observational studies, registry analyses, case series, case reports, and letters containing original clinical data. One additional author-known letter was screened using the same eligibility criteria.d. Findings were synthesized narratively. Results Forty-one reports were included. IARs ranged from mild transient symptoms to severe hypersensitivity reactions, including anaphylaxis. Larger trials and cohorts mainly provided frequency and safety data, whereas registry and case-based reports provided the most detailed management evidence. In the French Pompe Registry, rechallenge was successful in all 9 rechallenged patients using premedication, modified infusion regimens, or desensitization. Adult case reports further supported specialist-guided desensitization or individualized continuation strategies in selected high-risk patients. Anti-rhGAA IgG titers were associated with IAR risk in some adult cohorts, but their clinical significance in LOPD appears limited and should not be equated with IgE-mediated allergy. Home infusion appeared feasible in carefully selected stable adults with standardized protocols and escalation pathways. Conclusions IARs during ERT in LOPD do not necessarily preclude treatment continuation. Management should be adapted to reaction severity, recurrence, and suspected mechanism, with immediate patient safety taking priority. Switching between ERT products requires individual benefit-risk assessment; recurrent or severe reactions should prompt a structured plan before re-exposure, including allergologic or immunologic evaluation where appropriate. We propose a non-validated, expert-proposed clinical algorithm to support consistent IAR management in routine care.
