Natural History Charts

Infantile-Onset Natural History

The natural history of infantile-onset Pompe disease has been assessed using several study populations. Investigators at the Department of Clinical Genetics at Erasmus University in Rotterdam diagnosed 20 patients in the Netherlands between 1980 and 1988; the same group identified 133 cases reported in the literature viaa Medline search.1 By surveying physicians for cases with documented GAA deficiencyand symptom onset by 12 months of age, a retrospective chart review assessed 168 worldwide cases.2
Consistent results regarding the natural history of infantile-onset Pompe disease were obtained for each group of patients. The median age of first symptoms ranged from 1.6 to 2.0 months; the median age at diagnosis ranged from 4.5 to 5.3 months; and the median age at death ranged from 6.0 to 8.7 months.1,2 Data from these populations, originated across diverse geographical areas, establish a universal description of the natural history of infantile-onset Pompe disease as a rapidly progressive and ultimately fatal condition.

References

1. van den Hout HMP, Hop W, van Diggelen OP, et al. The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics. 2003;112:332-340.

2. Kishnani, Priya. Data on file.Genzyme Corporation: Cambridge, MA 02142.

Late-Onset Natural History

Three prospective studies have been conducted to evaluate patients either physically or biochemically/genetically illustrate the heterogeneity in the manifestations of lateonset Pompe disease.1 Although that heterogeneity may stem from the multiple mutations described in the GAA gene, it is problematic to establish valid correlations between genotype and phenotype of the disease.2 However, it has been possible to define patterns of symptom progression.1

Mellies et al evaluated 20 adult patients with late-onset Pompe disease. The average age was 46.7 years. The predominant symptom in all subjects was weakness of limb muscles.1 About one half of the patients developed respiratory symptoms. In these adult patients, symptoms occurred at a mean age of 36.3 years and were diagnosed at an average of 5.1 years later. The time from first symptoms of muscular weakness to ventilation averaged 11.3 years.

Similar results were obtained in a retrospective evaluation of US patients with lateonset Pompe disease. In this study, a 60-minute scripted interview was administered to 15 patients and their caregivers. The cohort included 10 men and 5 women, with a mean age of 46.9 years (range, 33 to 64 years). All were Caucasian. Milestones reported include: first symptom onset, mean age 30 years; muscle weakness, mean age 30.7 years; diagnosis at 34.7 years; progression to Bi-level Positive Airway Pressure at 36.9 years; and progression to wheelchair use at 41.4 years.3

The Late Onset Pompe Observational Study (LOPOS) evaluated 58 patients with late onset Pompe disease. The objective was to collect prospective, observational data to use to optimize the design of future clinical studies assessing the effects of enzyme replacement therapy with recombinant human acid alpha-glucosidase (rhGAA) in treating late-onset Pompe disease. This was a year-long, multi-center,multi-national study to assess the natural history of late-onset Pompe disease with evaluations at 1, 3, 6, and 12 months.4

The wide range in age and nature of the initial manifestations observed in these reports provides further evidence of the heterogeneous spectrum of late-onset Pompe disease.

References

1. Mellies U, Ragette R, Schwake C, et al. Sleep-disordered breathing and respiratory failure in acid maltase deficiency. Neurology. 2001;57:1290-1295.

2. Laforet P, Nicolino M, Eymard B, et al. Juvenile and adult-onset acid maltase deficiency in France. Genotype-phenotype correlation. Neurology. 2000;55: 1122-1128.

3. Data on file. Genzyme Corporation: Cambridge, MA 02142.

4. Data on file. Genzyme Corporation: Cambridge, MA 02142.