Clinical Impacts

Pompe disease presents as a broad phenotypic continuum, which is related to the residual acid α-glucosidase (GAA) activity level, ranging from rapidly fatal to slower progressive types.1,3 

As a general rule, the lower the residual enzyme activity level, the earlier the onset, the faster the progression and the worse the prognosis.2

Classic infantile-onset Pompe disease occurs soon after birth and is characterised by cardiomyopathy, cardiorespiratory failure and severe, generalized hypotonia.4 If not diagnosed and early treated, the infants rarely survive beyond the first year of life.

By contrast, in the non-classical infantile-onset form cardiomyopathy is less severe and survival somewhat longer.Late-onset Pompe disease generally has a milder phenotype and can present with symptoms any time after age 1 year.

It is characterised by skeletal myopathy usually in a limb-girdle distribution, and is associated with less cardiac involvement and a more protracted disease course, but eventually leads to respiratory failure.2, 4 The significant skeletal muscle involvement, with gradually progressing myopathy and respiratory insufficiency, is such that most patients require the use of a wheelchair and ventilatory assistance, both of which negatively impact quality of life.1,7

Analysis of data from 53 patients with Pompe disease (age range 0-64 years) has shown that patient’s health and functional status is often already severely impaired at the time of their diagnosis:7

  • Classic infantile-onset patients – cardiac function, hearing, muscle strength and motor development were all impaired, supplemental oxygen (36%) and nasogastric tubefeeding (64%) were required.7
  • Late-onset patients – advanced muscle weakness and impaired respiratory function, causing varying degrees of handicap, respiratory support (14% of adults) and use of a wheelchair (7% of adults) were required.7

References

  1. 1.van der Beek NA, de Vries JM, Hagemans ML, et al. Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study. Orphanet J Rare Dis. 2012;7:88.
  2. 2.Herzog A, Hartung R, Reuser AJ, et al. A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations. Orphanet J Rare Dis. 2012;7:35.
  3. 3.van der Ploeg AT, Reuser AJJ. Pompe's disease. The Lancet. 2008;372:1342-53.
  4. 4.Lim JA, Li L, Raben N. Pompe disease: from pathophysiology to therapy and back again. Front Aging Neurosci. 2014;6:177.
  1. 5.Manganelli F, Ruggiero L. Clinical features of Pompe disease. Acta Myol. 2013;32:82-4.
  2. 6.Kemper AR. The Condition Review Workgroup. Evidence Report: Newborn Screening For Pompe Disease. 2013. [cited 17/12/2015] Available here.
  3. 7.Rigter T, Weinreich SS, van El CG, et al. Severely impaired health status at diagnosis of Pompe disease: a cross-sectional analysis to explore the potential utility of neonatal screening. Mol Genet Metab. 2012;107:448-55.