Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: experiences from a nationwide newborn screening programme.

BACKGROUND: Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres. METHODS: In this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups. RESULTS: The average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects. CONCLUSION: Very early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres.

Very Early Treatment for Infantile-Onset Pompe Disease Contributes to Better Outcomes.

OBJECTIVE: To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies. METHODS: In this nationwide program, 669,797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital. RESULTS: After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid α-glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6 ± 1.3 months, the same age as normal children. CONCLUSIONS: ERT for patients with IOPD should be initiated as early as possible before irreversible damage occurs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes.

A large-scale nationwide newborn screening program for Pompe disease in Taiwan: towards effective diagnosis and treatment.

The aim of this study was to: (a) analyze the results of a large-scale newborn screening program for Pompe disease, and (b) establish an effective diagnostic protocol to obtain immediate, valid diagnosis of infantile-onset Pompe disease (IOPD) to promote earlier treatment and better outcomes. In this study, 402,281 newborns were screened for Pompe disease from January 1, 2008 to May 1, 2012. Infants with low acid α-glucosidase (GAA) activity were referred to Taipei Veterans General Hospital for diagnostic confirmation. Physical examination, biochemical parameter (creatine kinase [CK], alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase), and echocardiogram assessments were performed immediately to effectively differentiate IOPD from suspected late-onset Pompe disease (LOPD) or false-positive cases with pseudodeficiency mutation. Six infants with IOPD all presented with hypotonia, extremely low GAA enzyme activity (≤0.5 µmol/L/hr) in initial dried blood spot analysis, high CK (≥250 U/L), and high left ventricular mass index (LVMI, ≥80 g/m(2)). By analyzing these parameters, IOPD was distinguished effectively and immediately from suspected LOPD and false-positive cases. Except for the first referred case, five of the infants with IOPD received first-time enzyme replacement therapy (ERT) within 4 hr of admission and exhibited marked improvement. Our findings indicate that certain clinical manifestations (hypotonia, high CK, enlarged LVMI, and extremely low GAA enzyme activity in initial dried blood spot analysis) can help in the rapid and effective differentiation of patients with IOPD from other patient with low GAA activity. Such differentiation allows for the early application of first-time ERT and leads to better outcomes.

Very rare condition of multiple Gaucheroma: A case report and review of the literature.

BACKGROUND: This study presented a 3 years old boy with Gaucher disease (GD) who was treated with enzyme replacement therapy (ERT) for 19 months and then developed multiple Gaucheroma. Review of literature was performed simultaneously. METHODS: The medical chart and literature were reviewed. A boy presented at the age of 15 months with anemia, thrombocytopenia, and hepatosplenomegaly. GD was confirmed by enzyme assay and gene mutations. ERT was administered right after the diagnosis. When the boy was 3 years old, multiple masses were discovered during a regular checkup abdominal MRI and biopsy revealed Gaucheroma. We also reviewed 20 GD patients with Gaucheroma and Gaucher cell infiltrated lymphadenopathies. CONCLUSION: Gaucheroma is a rare condition of regularly treated GD patients. This patient even showed poor response to doubled ERT doses. The imaging studies are necessary for Gaucher patients to detect Gaucheroma and determine their malignancy. Regular checkups are recommended in all GD patients even with regular treatment, due to the possibility of having deteriorating change, like Gaucheroma.

Very rare condition of multiple Gaucheroma: A case report and review of the literature.

BACKGROUND: This study presented a 3 years old boy with Gaucher disease (GD) who was treated with enzyme replacement therapy(ERT) for 19 months and developed multiple Gaucheroma. The literature was reviewed. METHODS: The medical chart and literature were reviewed. A boy presented at the age of 15 months with anemia, thrombocytopenia, and hepatosplenomegaly. Enzyme assay and gene mutations confirmed GD. ERT was administered. When the boy was 3 years old, multiple masses were discovered from abdominal MRI and biopsy revealed Gaucheroma. We reviewed 20 GD patients with Gaucheroma and Gaucher cell infiltrated lymphadenopathies. CONCLUSION: Gaucheroma is a rare condition in regularly treated GD patients. This patient showed poor response to doubled ERT doses. The imaging studies are necessary for Gaucher patients to detect Gaucheroma and determine their malignancy. Regular checkups are recommended in all GD patients even with ERT treatment, due to the possibility of having a deteriorating change, like Gaucheroma.