Transforming the clinical outcome in CRIM-negative infantile Pompe disease identified via newborn screening: the benefits of early treatment with enzyme replacement therapy and immune tolerance induction.

Abstract

PURPOSE:

To assess the magnitude of benefit to early treatment initiation, enabled by newborn screening or prenatal diagnosis, in patients with cross-reactive immunological material (CRIM)-negative infantile Pompe disease (IPD), treated with enzyme replacement therapy (ERT) and prophylactic immune tolerance induction (ITI) with rituximab, methotrexate, and intravenous immunoglobulin (IVIG).

METHODS:

A total of 41 CRIM-negative IPD patients were evaluated. Among patients who were treated with ERT + ITI (n = 30), those who were invasive ventilator-free at baseline and had ≥6 months of follow-up were stratified based on age at treatment initiation: (1) early (≤4 weeks), (2) intermediate (>4 and ≤15 weeks), and (3) late (>15 weeks). A historical cohort of 11 CRIM-negative patients with IPD treated with ERT monotherapy served as an additional comparator group.

RESULTS:

Twenty patients were included; five, seven, and eight in early, intermediate, and late treatment groups, respectively. Genotypes were similar across the three groups. Early-treated patients showed significant improvements in left ventricular mass index, motor and pulmonary outcomes, as well as biomarkers creatine kinase and urinary glucose tetrasaccharide, compared with those treated later.

CONCLUSION:

Our preliminary data suggest that early treatment with ERT + ITI can transform the long-term CRIM-negative IPD phenotype, which represents the most severe end of the Pompe disease spectrum.

• Authors: Cindy Li, Ankit K Desai, Punita Gupta, Katherine Dempsey, Vikas Bhambhani, Robert J Hopkin, Can Ficicioglu, Pranoot Tanpaiboon, William J Craigen, Amy S Rosenberg, Priya S Kishnani
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 23 Issue 5 Pg. 845-855 (05 2021) ISSN: 1530-0366 [Electronic] United States
• PMID: 33495531 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Glucosidases

Topics

• Enzyme Replacement Therapy
• Female
• Glycogen Storage Disease Type II (diagnosis, drug therapy, genetics)
• Humans
• Immune Tolerance
• Infant, Newborn
• Neonatal Screening
• Pregnancy
• Treatment Outcome
• alpha-Glucosidases (genetics, therapeutic use)