Ten years of the international Pompe survey: patient reported outcomes as a reliable tool for studying treated and untreated children and adults with non-classic Pompe disease.

Pompe disease is a rare, progressive lysosomal storage disorder for which enzyme therapy (ERT) became available in 2006. Four years earlier, the IPA/Erasmus MC survey, an international longitudinal prospective survey, was established to collect information on the natural course of the disease and its burden on patients. The survey is a collaboration between Erasmus MC University Medical Center and the International Pompe Association (IPA) and comprises an annual questionnaire that was specifically designed to assess the symptoms and problems of the disease. Here we review our results of over 10 years of follow-up, and discuss the survey's contribution to the field. Tracking 408 Pompe patients between 2002 and 2013, the cumulative data reveals the broad range of clinical manifestations that interfere with patients' lives. The survey allowed us to quantify the rate of disease progression and the positive effects of ERT on patients' quality of life, fatigue, and participation in daily life. Furthermore, it showed for the first time that survival is reduced in adult Pompe disease and improved by ERT. Our results show that a patient survey can serve as a valuable and reliable tool for obtaining quantifiable information on the natural course of a rare disease and on the effects of therapy in a large cohort over a very long time. Most importantly, by working with patient reported outcomes, the survey provides the data that is truly relevant to the patient and complementary to clinical datasets.

Pain in adult patients with Pompe disease: a cross-sectional survey.

BACKGROUND: Pompe disease is a rare hereditary metabolic myopathy caused by a deficiency of acid-α-glucosidase. We investigated the presence and severity of pain and its interference with daily activities in a large group of adults with Pompe disease, who we compared with an age-matched control group. METHODS: Data were collected in a cross-sectional survey in Germany and The Netherlands. Pain was assessed using the short-form brief pain inventory (BPI). Patients also completed the Short Form-36 item (SF-36v2), the Hospital Anxiety and Depression Scale (HADS) and the Rotterdam Handicap Scale (RHS). RESULTS: Forty-five percent of the 124 adult Pompe patients reported having had pain in the previous 24h, against 27% of the 111 controls (p=0.004). The median pain severity score in Pompe patients reporting pain was 3.1 (on a scale from 0 to 10), indicating mild pain; against 2.6 amongst controls (p=0.06). The median score of pain interference with daily activities in patients who reported pain was 3.3, against 1.3 in controls (p=0.001). Relative to patients without pain, those with pain had lower RHS scores (p=0.02), lower SF-36 Physical and Mental component summary scores (p<0.001 and p=0.049), and higher levels of depression and anxiety (p=0.005 and p=0.003). CONCLUSIONS: To date, this is one of the largest studies on pain in a specific neuromuscular disorder. Nearly one in two Pompe patients had experienced pain in the previous 24h. Although pain severity and its interference with daily life were mild, pain was related to a reduced quality of life, less participation in daily life, and greater depression and anxiety. Its management should therefore be seen as part of clinical practice involving Pompe patients.

Improved glycemic control increases fasting plasma acylation-stimulating protein and decreases leptin concentrations in type II diabetic subjects.

Acylation-stimulating protein is an adipocyte-derived protein that has recently been suggested to play an important role in the regulation of triglyceride storage. To date, little information has been reported with regard to fasting acylation-stimulating protein levels and its relation to metabolic control, leptin, and/or lipids in subjects with diabetes mellitus. We therefore evaluated fasting acylation-stimulating protein, leptin, and lipid levels before and 4 months after improving glycemic control with sulfonylurea treatment in a group of poorly controlled obese women with type 2 diabetes and in age- and body mass index-matched nondiabetic obese women. Fasting plasma acylation-stimulating protein (49.67 +/- 19.73 vs. 48.49 +/- 20.70 nmol/liter) and leptin concentrations (33.7 +/- 23.2 vs. 26.2 +/- 10.6 ng/ml) were not significantly different between the groups. Improvement of glycemic control produced parallel falls in fasting blood glucose and hemoglobin A1c. Plasma leptin concentrations were also significantly reduced (33.69 +/- 23.2 vs. 22.73 +/- 11.26 ng/ml; P = 0.036), whereas fasting acylation-stimulating protein concentrations were significantly increased after treatment (48.49 +/- 20.70 vs. 72,82 +/- 29,72 nmol/liter; P = 0.004). Nevertheless, lipids and apolipoprotein B did not significantly improve. We could not find any correlation between elevated acylation-stimulating protein levels and changes in body mass index, glucose, insulin, hemoglobin A1c, leptin, or lipid levels. Similarly, the decrement in circulating leptin levels observed after treatment did not correlate with changes in the levels of glucose, insulin, hemoglobin A1c, or any lipid parameters. We conclude that improved glycemic control increases fasting acylation-stimulating protein and decreases leptin concentrations, but not corrects critical lipid abnormalities in type 2 obese diabetic subjects. Moreover, altered plasma acylation-stimulating protein levels are not associated with changes in body mass index or lipid, leptin, insulin, or glucose levels. Thus, our findings suggest that improved glycemic control or insulin resistance is not responsible for abnormal fatty acid trapping, and failure of lipids to improve after treatment in our patients is consistent with the acylation-stimulating protein resistance concept.