Several publications have been released on methods to detect Pompe patients who were previously suspected of having another type of neuromuscular disease. In this article, the experiences in Denmark, the Czech Republic, and Brazil are discussed.
A Danish publication reveals that in 2008 only 2 late onset Pompe patients were diagnosed in a population of 5.5 million. It was, therefore, suspected that the condition might be overlooked. To find Pompe patients a screening program was set up in the largest neuromuscular clinic and respiratory center in Denmark. Inclusion criteria were: unexplained hyper-CK-aemia and myopathy; unclassified Limb-girdle muscular dystrophy (LGMD); and unexplained, restrictive respiratory insufficiency. Via medical journals 123 patients were found who met the inclusion criteria, 60 patients consented to screening using dried blood spots (DBS). From the screening 3 late onset Pompe patients were found who were previously diagnosed with unclassified LGMD.
Conclusion: The results suggest that adult Pompe disease in Denmark is under-diagnosed. Dried blood spot is a cheap and effective method to screen for Pompe Disease in patients with a LGMD phenotype.
Source: Journal of Neuromuscular Disorders 2011, Pompe disease in persons with unclassified Limb-girdle muscular dystrophy, E.H. Husu, N. Preisler, K. Madsen, R. Hansen, Z. Lukacs, M. Laub, M. Dunoe, H. Andersen, L. Vinge, J. Vissing.
At the time the screening program was initiated, no late onset Pompe patient had been discovered in the Czech population, despite the fact that the incidence of all forms of Pompe disease is estimated to be 1:40,000. It was therefore hypothesized that patients were being misdiagnosed, especially with Limb girdle muscular dystrophy (LGMD). The aim of the screening program was to uncover undiagnosed Pompe patients among persons with muscle weakness of uncertain or unknown etiology. The screening program started in May 2008. Three hundred screening sets with information about Pompe disease and diagnostic filter papers were sent to Czech neurologists. Two hundred sets were delivered directly to patients who were members of the Czech Muscular Dystrophy Association. The information campaign was focused towards the medical staff using lectures and articles for neurologists. For patients, the information campaign was conducted through a combination of lectures at patient meetings and articles in patient magazines. By December 2009, 182 specimens were returned and examined (36% return rate). Three Pompe patients were found and confirmed. Two of these patients had presented with limb girdle weakness and one patient had presented with severe trunk muscle weakness.
Source: Journal of Neuromuscular Disorders 2010, Screening program for adult Pompe disease in Czech Republic, S. Vohanka, H. Oslejskova, J. Hlavata, Z. Lukacs.
A study performed in Cuiaba, Brazil was aimed to identify patients with Pompe disease among patients with progressive muscle weakness attending the neurology clinic at Cuiaba University Teaching Hospital. This observational, cross-sectional study consisted of descriptive analyses of 48 patients receiving care at the department of neurology, peadiatric neurology and genetic clinics in Cuiaba during 2010. To test the enzyme activity in potential patient a dried blood spot (DBS) sample on filter was used. This sample was obtained from all patients with progressive muscle weakness, history of frequent falls or patients whose physical examination revealed reduction in muscle strength. In total, 48 patients were evaluated and one patient with Pompe disease was found. The diagnosis was confirmed by fibroblast culture and gene mutation testing.
Source: Journal of Neuromuscular Disorders 2011, Analysis of the screening process for Pompe disease at the Cuiaba University Teaching Hospital, Brazil in 2010, H.H. Sigueira, T.A. Felicio, R.S. Borges, F.B. Lima, M.F. Galera, J.S. Dalbem.
From these studies it is interesting to learn Pompe patients can be identified amongst the limited population of patients who present with clinical symptoms such as limb girdle weakness or respiratory weakness. Finding Pompe patients is essential now that enzyme replacement therapy is available. One could wonder what would have happened to these people if they were not diagnosed via the screening program using dried blood spot testing.
It is especially important to notice that the Czech Muscular Dystrophy Association has played an important role in the process of diagnosing Pompe patients among their members who meet certain criteria. After a presentation given by the International Pompe Association (IPA) at the Central & Eastern European Genetic Network (CEE GN) meeting in Prague (January 2008) where the topic of misdiagnosis was addressed, the Czech Muscular Dystrophy Association took the initiative to take up the challenge of misdiagnosis. The result of their hard work is that 3 Pompe patients have been diagnosed and are receiving treatment. These are patients who would otherwise still be untreated.
Author: Maryze Schoneveld van der Linde
Editor: Tiffany House
With special thanks to Ron Eggers for his contribution