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. 2019 Jul 17;49(1):89-95.
doi: 10.1002/jmd2.12062. eCollection 2019 Sep.

Extent, impact, and predictors of diagnostic delay in Pompe disease: A combined survey approach to unveil the diagnostic odyssey

Florian B Lagler  1   2 , Angelika Moder  1 , Marianne Rohrbach  3 , Julia Hennermann  4 , Eugen Mengel  4 , Seyfullah Gökce  4 , Thomas Hundsberger  5 , Kai M Rösler  6 , Nesrin Karabul  7 , Martina Huemer  3   8   9
Affiliations

Extent, impact, and predictors of diagnostic delay in Pompe disease: A combined survey approach to unveil the diagnostic odyssey

Florian B Lagler et al. JIMD Rep. .

Abstract

Background: Early diagnosis is of substantial benefit for patients with Pompe disease. Yet underdiagnosing and substantial diagnostic delay are still frequent and the determinants of this are unknown. This study is the first to systematically investigate the diagnostic odyssey in Pompe disease from patients', parents', and physicians' perspectives.

Methods: Patients with infantile or late onset Pompe disease, their parents as well as their metabolic experts were invited to fill in respective surveys. The survey addressed perceived disease symptoms at onset and during the course of the disease, specialties of involved physicians, activities of patient-initiated search for diagnosis and the perceived impact of time to diagnosis on outcome. Results of experts' and patients'/parents' surveys were compared and expressed by descriptive statistics.

Results and discussion: We collected data on 15 males and 17 females including 9 infantile and 23 late onset Pompe patients. All received the correct diagnosis at a metabolic or musculoskeletal expert center. Patients with direct referral to the expert center had the lowest diagnostic delay, while patients who were seen by several physicians, received the correct diagnosis after 44%-200% longer delay. The proportion of direct referral varied strongly between pediatricians (57%) and other disciplines (18%-36%).

Conclusion: Our study highlights a substantially larger diagnostic delay in Pompe patients that are not directly referred to expert centers for diagnostic work. Our findings may be used to develop more successful strategies for early diagnosis.

Synopsis: Diagnostic delay in Pompe disease is substantial particularly in patients that are not directly referred to expert centers for diagnostic workup, so facilitating direct referral may be a new strategy for early diagnosis.

Keywords: Pompe disease; diagnostic delay; diagnostic odyssey; expert centers; initial symptoms; patient perspective; survey.

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Conflict of interest statement

The authors of this manuscript declare no conflict of interests but disclose the following: FBL has received honoraria and travel reimbursement from Actelion, BioMarin, Merck Serono, Sanofi Genzymem and Shire. AM has no conflict of interest. MR has received speaker honoraria from Genzyme and Shire. JH has received travel expenses from Shire, Sanofi/Genzyme, and Biomarin as well as honoraria from Shire. Her institute has received research/education funding from Shire. EM has received honoraria and/or consulting fees from Actelion, Alexion, BioMarin, Orphazyme, Sanofi Genzyme, and Shire. SG received travel expenses for presentations given at medical conferences, by Genzyme/Sanofi, Alexion, and Shire. TH received speakers' honoraria and travel reimbursement from Genzyme Switzerland. KR received honoraria as a consultant and an unrestricted research grant (not related to the present work) by Genzyme/Sanofi. He also received honoraria and travel expenses for presentations given at medical conferences by Genzyme/Sanofi and Shire. NK has received consulting fees from BioMarin, Sanofi Genzyme, and Shire. MH has received speaker honoraria from Genzyme, SOBI, and Shire and an unrestricted research grant (not related to the present work) from Nutricia Metabolics.

Figures

Figure 1
Figure 1
Rank correlation (Spearman) of diagnostic delay and age of onset
Figure 2
Figure 2
Diagnostic delay by HCP involved. The figure shows which specialists (lower part) have been consulted for the initial signs and symptoms of Pompe disease, the number of patients directly referred to an expert center (straight arrows in dark colors), and the number of patients who underwent a diagnostic odyssey (winded arrows in light colors). In the top part the median diagnostic delay in months is compared between the latter two groups indicating approximately a duplication of delay by the diagnostic odyssey
Figure 3
Figure 3
Symptoms as specified by parents/patients vs experts
See this image and copyright information in PMC

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