Progression and prognosis

Pompe disease is rapidly progressive in infants, usually proving fatal in the first year of life without treatment.

Pompe disease is rapidly progressive in infants, usually proving fatal in the first year of life without  treatment Kishnani PS, Howell RR. Pompe disease in infants and children. J Pediatr 2004; 144(5 Suppl): S35-S43 . The course of the condition is far more variable in older children and adults, but it remains relentlessly progressive, resulting in significant morbidity and often premature  mortality 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 2005; 128:671-7. 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. Gungor D, de Vries JM, Hop WC, et al. Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy. Orphanet J Rare Dis 2011; 6: 34 .  Thus, Pompe disease is a single condition with variable rates of progression and symptom onset. All Pompe disease phenotypes are caused by mutations within the same gene.

Natural history

Disease course in infants

In the studies presented in the graph below, diagnosis was delayed by an average of nearly 3 months, while median age of death was less than 9  months 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. 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. . This highlights the serious problem of delayed diagnosis in infants with Pompe disease, given the rapid progression of the condition in this patient population.

Age of symptom onset, diagnosis and death in infants with Pompe  disease 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. 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.

Age of symptom onset, diagnosis and death in infants with Pompe  disease
Adapted from Van den Hout et al,  2005 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. and Kishnani et al,  2006 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. .

Disease course in children and adults

Hagemans et al investigated the course of Pompe disease in 54 patients (mean age 48.6 years; range 3.9–81.2  years 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 2005; 128:671-7 ). Of these, 40 patients presented information on the time between first visiting a doctor with complaints relating to Pompe disease and diagnosis of the condition. For 28% of these patients, diagnosis took as long as 5 to 30 years, while 20% had to wait between 1 and 5 years to be  diagnosed 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 2005; 128:671-7 . This exemplifies the problem of delayed diagnosis in children and adults, given the relentless progression of Pompe disease and the importance of early diagnosis for optimal management. 

Age distribution for specific events in the course of Pompe  disease 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 2005; 128:671-7

Age distribution for specific events in the course of Pompe disease

Adapted from Hagemans et al,  2005 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 2005; 128:671-7

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. In the classic infantile form of the disease for example, untreated Pompe disease has been uniformly  lethal 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 .

Outcomes are much harder to predict for patients who first show symptoms of Pompe disease as children, adolescents or adults. Overall, the disease’s relentless progression results in significant morbidity and adverse impact on quality-of-life, such as dependence on wheelchairs and/or respiratory support. Patient life-expectancy varies. While cardiac involvement is rare in non-infantile patients, premature death – usually from respiratory failure – is not  uncommon 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 2005; 128:671-7. 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. Gungor D, de Vries JM, Hop WC, et al. Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy. Orphanet J Rare Dis 2011; 6: 34 .