Table 1.
Baseline demographic characteristics of IOPD patients that received TLD-MTX protocol
| Patient | Sex | GAA pathogenic variants | Age at start of ERT | ERT dose and frequency1 | Route of MTX administration | TLD-MTX Protocol deviation | |
|---|---|---|---|---|---|---|---|
| Variant 1 | Variant 2 | ||||||
| IOPD1 | M | c.953T>C | c.1292_1295dupTGCA | 0.9 months | 20 mg/kg weekly | MTX administered SC | Only one dose administered in 2nd cycle of MTX |
| p.Met318Thr | p.Gln433AlafsX74 | ||||||
| IOPD2 | M | c.1004G>A | c.1841C>A | 3.3 months | 20 mg/kg EOW | NA | None |
| p.Gly335Glu | p.Thr614Lys | ||||||
| IOPD3 | M | c.1118T>G | c.1118T>G | 4.0 months | 20 mg/kg EOW | MTX administered SC | Only one dose administered in 2nd & 3rd cycle each and additional 4th cycle was administered |
| p.Leu373Arg | p.Leu373Arg | ||||||
| IOPD4 | F | c.2560C>T | c.1466A>G | 0.8 months | 20 mg/kg EOW | MTX administered SC | 3rd cycle of MTX & ERT was administered on Week 5 instead of Week4 |
| p.Arg854X | p.Asp489Gly | ||||||
| IOPD5 | F | c.665T>G | c.1437+2T>C | 3.5 months | 20 mg/kg weekly | MTX administered SC | None |
| p.Val222Gly | Deletion p.Asp443_Lys479del | ||||||
| IOPD6 | F | c.1114C>T | c. 1979G>A | 11.2 months | 20 mg/kg EOW | MTX administered PO | None |
| p. His372Tyr | p.Arg660His | ||||||
| IOPD7 | F | c.2456G>C | c.2456G>C | 1.2 months | 20 mg/kg EOW | MTX administered SC | None |
| p.Arg819Pro | p.Arg819Pro | ||||||
| IOPD8 | F | c.525delT | c.2297A>C | 4.6 months | 20 mg/kg EOW | MTX administered SC | 3rd cycle of MTX & ERT was administered on Week 5 instead of Week4 |
| p.Glu176Argfs*45 | p.Tyr766Ser | ||||||
| IOPD92 | F | c.1A>G | c.1A>G | 12.9 months | 20 mg/kg EOW | MTX administered SC | None |
| Initiator codon | Initiator codon | ||||||
| IOPD10 | F | c.1942G>A | c.1942G>A | 1.7 months | 20 mg/kg EOW | MTX administered SC | 3rd dose of 3rd cycle of MTX was skipped |
| p.Gly648Ser | p.Gly648Ser | ||||||
| IOPD11 | F | c.1447G>A | c.2560C>T | 13.5 months | 20 mg/kg EOW | 3rd dose of 3rd cycle was given orally, all other MTX administered SC | None |
| p.Gly483Arg | p.Arg854X | ||||||
| IOPD12 | M | c.1A>G | c.2234T>C | 0.7 months | 20 mg/kg EOW | MTX administered SC | None |
| Initiator codon | p.Leu745Pro | ||||||
| IOPD13 | F | c.1979G>A | c.2560C>T | 4.5 months | 20 mg/kg EOW3 | MTX administered SC | None |
| p.Arg660His | p.Arg854X | ||||||
| IOPD14 | F | c.525delT | c.1979G>A | 4.0 months | 20 mg/kg EOW | MTX administered PO | 1st MTX dose of 3rd cycle was skipped |
| p.Glu176Argfs*45 | p.Arg660His | ||||||
TLD-MTX, transient low-dose methotrexate, ANC, absolute neutrophil count; IOPD, infantile-onset Pompe disease, EOW, every other week, PO, orally (per os), SC, subcutaneous, ERT, enzyme replacement therapy.
1
ERT dose and frequency was determined based on the clinical judgement of the treating physician.
2
Patient IOPD9 is CRIM-negative.
3
ERT dose was changed to 40 mg/kg/weekly after two infusions.