Characteristics of Patients With Late-Onset Pompe Disease in France: Insights From the French Pompe Registry in 2022

Abstract

Background and objectives: The French Pompe disease registry was created in 2004 for study of the natural course of the disease in patients. It rapidly became a major tool for assessing the long-term efficacy of enzyme replacement therapy (ERT) after the market release of alglucosidase-alfa.

Methods: Approximately 10 years after publication of the baseline characteristics of the 126 initial patients of the French Late-Onset Pompe Disease registry, we provide here an update of the clinical and biological features of patients included in this registry.

Results: We describe 210 patients followed at 31 hospital-based French neuromuscular or metabolic centers. The median age at inclusion was 48.67 ± 14.91 years. The first symptom was progressive lower limb muscle weakness, either isolated (50%) or associated with respiratory symptoms (18%), at a median age of 38 ± 14.9 years. At inclusion, 64% of the patients were able to walk independently and 14% needed a wheelchair. Positive associations were found between motor function measure, manual motor test, and 6-minute walk test (6MWT) results, and these parameters were inversely associated with the time taken to sit up from a lying position at inclusion. Seventy-two patients had been followed for at least 10 years in the registry. Thirty-three patients remained untreated a median of 12 years after symptom onset. The standard ERT dose was administered for 177 patients.

Discussion: This update confirms previous findings for the adult population included in the French Pompe disease registry, but with a lower clinical severity at inclusion, suggesting that this rare disease is now diagnosed earlier; thanks to greater awareness among physicians. The 6MWT remains an important method for assessing motor performance and walking ability. The French Pompe disease registry provides an exhaustive, nationwide overview of Pompe disease and can be used to assess individual and global responses to future treatments.

Figure 1. Clinical Topography of Muscle Weakness

Box plots are drawn for subscores of the MRC scale. The median is indicated by the line bisecting the box. The box represents the middle 50% of scores: the interquartile range. The upper and lower whiskers represent the minimum and maximum scores. The most severe weakness was that for hip muscles. The median score was below 3/5 for flexion, extension, abduction, and adduction of the hips, corresponding to an inability to move actively against gravity. Axial weakness predominated for trunk muscles, with a median score of 2/5, corresponding to active movement in the absence of gravity. Distal motor function was better preserved, with a median score of 4/5 or more for the wrist, ankle, elbow, and knee. L = left; MRC = Medical Research Council; R = right.

Figure 2. Correlogram of All the Main Clinical Parameters of Patients at Inclusion

Blue indicates a positive correlation, and red indicates an inverse correlation. The intensity of the color indicates the strength of the correlation. 6MWT = 6-minute walk test; CPK = Creatine Phosphokinase; FSS = Fatigue Severity Scale; FVC = forced vital capacity; MEP = maximal expiratory pressure; MFM = motor function measurement; MIP = maximal inspiratory pressure; MMT = manual muscle test.

Figure 3. Survival Curves for Walking Ability and Respiratory Function Status for Adult Patients With Pompe Disease in the French Registry

Time in years from the start of ERT is plotted on the x-axis, whereas the probability of no progression or the proportion of individuals displaying stabilization is shown on the y-axis. The lines are the survival curves. Vertical drops in these curves correspond to events. The number of patients at risk is indicated below. At time 0, the probability of no progression is 1.0 (100% of the patients are in their baseline state). At 5 years, the probability of no progression is approximately 70% for walking ability and 80% for respiratory function status. Median survival is approximately 9.4 years for walking ability and 14.8 years for respiratory function status. ERT = enzyme replacement therapy.

Figure 4. Disease Course in Untreated Patients vs Patients Treated by ERT: Walking and Respiration

(A) Sitting FVC. At inclusion, the mean value for the untreated group was 3.36 ± 0.3 L; the mean value for the treated group was 0.75 ± 0.4 L lower, at 2.61 L (p = 0.056). Over time, the mean change in the untreated patients was −0.07 ± 0.009 (p < 0.001) and in the treated patients was 0.02 ± 0.01 L smaller, at −0.05 (p = 0.002). (B) Supine FVC. At inclusion, there was no significant difference between the 2 groups: the mean value for the untreated group was 2.95 ± 0.3 L and for the treated group was 0.82 ± 0.5 L lower, at 2.13 (p = 0.08). Over time, there was no significant difference in the changes observed between the 2 groups: the mean change for untreated patients was −0.07 ± 0.01 (p < 0.001) and for treated patients was 0.01 ± 0.01 L smaller, at −0.06 L (p = 0.40). (C) 6-MWT. At inclusion, there was no significant difference between the 2 groups: 444.6 ± 36.7 for the untreated group, 13.5 ± 46.6 lower, that is, 431.1 (p = 0.77) for the treated group. Over time, untreated patients remained stable with a coefficient of −0.15 ± 0.2; the slope for the treated patients was 0.85 ± 0.2, corresponding to a mean progression of −1.00 (p < 0.001). 6MWT = 6-minute walk test; ERT = enzyme replacement therapy; FVC = forced vital capacity.