Progression & Prognosis

Pompe disease affects patients of all ages and is always characterized by progressive degeneration of skeletal muscles (proximal and respiratory) and, in infants, cardiac muscle. The rate of progression varies, ranging from a rapidly progressive course that is usually fatal by one year of age,[1], [2] to a more variable but still relentless, progressive course resulting in significant morbidity and often premature mortality.[3-7] Typically, when the disease is manifested early in infancy, the rate of progression is very rapid, and without treatment the prognosis is poor. Children and adults usually display more gradual and variable rates of disease progression; however, the prognosis often remains unpredictable and poor.

Pompe disease is a single disease with variable rates of progression and symptom onset. This reflects the fact that all phenotypes are caused by mutations with in the same gene.[3,8]

Natural History

Some broad generalizations can be made about the natural history of Pompe disease, as illustrated in the graphs below.

Disease Course in Infants

Several studies have helped researchers assess the natural history of Pompe disease in infants; the following graph summarizes the results of three key studies:

 

All studies also demonstrated a significant delay (averaging 3.1 months) in the diagnosis of Pompe disease in infants—a critical finding considering the very rapid progression of the disease in this patient population. The average age of death is less than nine months.

Disease Course in Older Patients

In children and adults, Pompe disease is more heterogeneous. The following graph summarizes the results of three key studies:

  • Mellies clinical study of 20 adult patients[9]
  • Genzyme retrospective evaluation of 15 adult patients[10]
  • Genzyme prospective observational study[11]

 

Broad clinical patterns emerge for the wide range of clinical manifestations and rates of progression in these studies, including muscle weakness, respiratory insufficiency, and the eventual need for ventilator and ambulatory support.

Results from these and other studies suggest that among adults with Pompe disease, the diagnostic delay can be significant, averaging roughly seven years (but often much longer). During this time, the disease is relentlessly progressive and can cause significant morbidity and physical disability.

A Range of Outcomes

Pompe disease is always progressive, with continuing glycogen accumulation in target tissues. Although individual patient outcomes may vary, some general observations can be made.

Prognosis in Infants

In infants with cardiac hypertrophy, Pompe disease has been uniformly lethal, as shown in this graph:

 

Reprinted from Kishnani et al., 2006, with permission from Elsevier.[2]

The reported mean age of death of infants with Pompe disease is 6-8 months, with 75-95% of babies dying before age one year from cardiorespiratory failure.[1-3], [12]

Learn more about the specific clinical manifestations in infants with Pompe disease

Prognosis in Older Patients

Among older patients—those who first show symptoms as children, adolescents, or adults—outcomes are much harder to predict. The rate of progression can change suddenly without warning, and an abrupt clinical decline can occur at any time.[7]

Overall, the disease’s relentless progression results in significant morbidity and quality-of-life impact, such as dependence on wheelchairs and/or respiratory support.

Get more details on Pompe disease’s impact on patient quality of life

Patient life expectancy varies, and while cardiac involvement is rare, premature death (usually from respiratory failure) is not uncommon.[2, 7]

Learn more about the specific clinical manifestations in children and adults with Pompe disease

References
  1. Van den Hout HMP. The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatr 2003 Aug; 112 (2): 332-340.
  2. Kishnani PS, Hwu W-L, Mandel H, Nicolino M, Yong F, Corzo D. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006; 148:671-676.
  3. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid Alpha-glucosidase (Acid Maltase) Deficiency. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill, 2001. 3389-3420.
  4. Hagemans ML, Winkel LP, Van Doorn PA, et al. Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain 2006; 128:671-7.
  5. Hagemans ML, Winkel LP, Hop WC, Reuser AJ, Van Doorn PA, Van der Ploeg AT. Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology 2006; 64:2139-41.
  6. Hagemans ML, Hop WC, Van Doorn PA, Reuser AJ, Van der Ploeg AT. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology 2006; 66:581-3.
  7. Winkel LP, Hagemans ML, van Doorn PA, et al. The natural course of non-classic Pompe’s disease; a review of 225 published cases. J Neurol 2006; 252:875-84.
  8. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med 2006; 8:267-88.
  9. Mellies U, Ragette R, Schwake C, et al. Sleep-disordered breathing and respiratory failure in acid maltase deficiency. Neurology 2001 Oct 9; 57(7): 1290-5.
  10. Data on file. Genzyme Corporation: Cambridge, MA 02142
  11. Wokke J, Escolar D, Pestronk A, Jaffe K, Carter G, van den Berg L, et al. Clinical features of late-onset Pompe disease: A prospective cohort study. Muscle Nerve 2008;38:1236-45.
  12. Hagemans ML, Laforet P, Hop WJ, et al. Impact of late-onset Pompe disease on participation in daily life activities: evaluation of the Rotterdam Handicap Scale. Neuromusc Disord. 2007. 17(7):537-43.

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