MASSIVE DISEASE BURDEN IN INFANTS WITH GAUCHER DISEASE TYPE 1 AND TYPE 3: LONG-TERM OUTCOMES OF EARLY IMIGLUCERASE THERAPY

Early treatment initiation improves response in progressive genetic diseases; however, longitudinal data for infants with Gaucher disease (GD) treated before age two are limited. To report long-term outcomes for non-splenectomized children with Gaucher type 1 and type 3 from the International Collaborative Gaucher Group Registry who started imiglucerase before age 2y and had baseline and follow-up data. We report long-term outcomes for non-splenectomized children with Gaucher type 1 (GD1; N = 60) and type 3 (GD3; N=129) from the International Collaborative Gaucher Group Registry as of February 2025 who started imiglucerase before age 2y and had baseline and follow-up data. Median age at treatment initiation was 1.5 years for GD1 and 1.4 years for GD3. At baseline, patients with GD1 had a median (25th, 75th percentile) body weight (BW) of 9.1 kg (7.9, 10.1) and a combined liver and spleen volume of 15.1% (10.8, 16.8) of their BW. For children with GD3, median (25th, 75th percentile) BW was 9.5 kg (8.4, 10.4), and liver and spleen volume comprised 11.6% (8.2, 14.2) of their BW. Results are presented as median values (95% confidence interval [CI]) at baseline and percentage change (95% CI) from baseline to 2 years (Y2), 5 years (Y5), and 10 years (Y10) of imiglucerase treatment. In GD1, spleen volume (baseline: 36.5 multiples of normal [MN]; 9.7–42.2; n = 21) decreased by 38.1% (29.3–47.2; n = 16) in Y2, 58.3% (52.8–64.5; n = 12) in Y5 and 70.5% (50.5–92.1; n = 6) in Y10. In GD3, spleen volume (baseline: 31.1 MN; 21.5–37.8; n = 44) decreased by 47.9% (36.5–57.6; n = 34) in Y2, 61.4% (40.1–74.4; n = 25) in Y5 and 80.6% (72.3–91.5; n = 13) in Y10. In GD1, platelet count (baseline: 141.5 × 103/mm 3 ; 93.0– 220.0; n=38) increased by 40.4% (17.8–67.2; n = 35) in Y2, 25.6% (-11.4–55.9; n = 27) in Y5 and 35.5% (0.0–62.1; n=19) in Y10. In GD3, platelet count (baseline: 102.0 × 103/mm 3 ; 75.0–174.0; n = 87) increased by 100.1% (64.9–141.5; n = 76) in Y2, 125.4% (85.1–165.2; n = 63) in Y5 and 113.7% (34.4– 201.0; n = 42) in Y10. Early imiglucerase therapy profoundly changed the clinical trajectory for children with severe GD1 and GD3 presenting before two years of age, dramatically reducing the initial massive disease burden and enabling sustained normalization of organ size, and hematologic parameters. These robust outcomes compellingly advocate for early diagnosis and intervention as a vital strategy to transform the clinical course and prognosis of children with GD.