About Pompe Disease

Pompe Disease
A progressive, multisystemic, debilitation, and often fatal muscular disease
• Single disease continuum presenting with variable rates of progression
• Presentation ranges from a rapidly progressive course that is usually fatal by 1 year to variable and relentlessly progressive course resulting in significant morbidity and often premature mortality
• Skeletal and respiratory muscles, as well as cardiac muscles in infants, are more severely affected, leading to a significant burden of illness and diminished quality of life
• Lysosomal enzyme deficiency (acid alpha-glucosidase or GAA) results in progressive glycogen accumulation that may eventually lead to irreversible muscle damage, and premature death
• Also known as Acid Maltase Deficiency (AMD) or Glycogen Storage Disease Type II (GSD-II)
• Diagnosis can be confirmed by enzyme assay in tissue or blood

Pompe disease is inherited in an autosomal recessive manner, meaning that an affected individual must inherit an abnormal allele from both parents. Thus, the probability of carrier parents having a child with Pompe disease is one in four for each pregnancy.

Patients with Pompe disease have deficient lysosomal enzyme acid alpha-glucosidase(GAA) activity, which catalyzes the breakdown of glycogen to glucose in the lysosome. Without sufficient GAA activity, massive amounts of glycogen can accumulate in the lysosome, causing distention of this organelle.1 1. Hirschhorn R, Reuser AJJ. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Scriver C, Beaudet A, Sly W, et al., eds. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw Hill, 2001: 3389-3420.

Electron microscopy demonstrates the various features of baseline skeletal muscle pathology in an infantile Pompe patient (magnification 6500x image courtesy of Genzyme Pathology).

Most infants with Pompe disease have marked cardiomegaly due to glycogen accumulation in cardiac tissue. With permission from B. Byrne, MD

Infants with rapidly progressive Pompe disease have profound muscle weakness, which is shown by the characteristic head lag and frog-like posture of the legs.

Note the shortened PR interval and tall QRS complexes in this electrocardiogram of an infant with Pompe disease. With permission from B.Byrne, MD.

Median age at first symptoms (green), diagnosis (blue), death (yellow) are shown for two different populations of infants with Pompe disease. Van den Hout et al. 1 report on 133 cases described in the literature. Kishnani et al. 2 report on a retrospective chart review of 168 cases of infantile Pompe disease from around the world.

1. van den Hout HM, Hop W. Van Diggelen OP, et al. The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics 2003; 112:332-40.

2. Kishnani PD, Hwu W-L, Mandel H, Nicolino M, Young F, Corzo D. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006; 148:671-676.

Median age at disease onset (green) and at diagnosis (blue) are shown in a retrospective analysis of 225 children and adult Pompe patients from the medical literature conducted by Winkel et al. 1 Ranges for each age cohort are shown in parentheses below the median age.

1. Winkel LP, Hagenmans ML, van Doorn PA, et al. The natural course of non-classic Pompe’s disease; a review of 225 published cases. JNeurol2005; 252:875-84.

How Do You Get Pompe Disease?

Pompe disease is inherited as an autosomal recessive disorder. The term autosomal implies that males and females have an equal chance of being affected. Recessive means that in order to get Pompe disease, an individual has to inherit two faulty copies of the Pompe disease (GAA) gene. Children usually inherit 1 copy of any particular gene from each parent. The mutant GAA gene (trait) can be passed on from unaffected parents (carriers) to their children. The likelihood of children born from Pompe disease carrier parents to suffer the disease is 25% (1 out of 4). Parents who carry a faulty copy of the GAA gene also have a normal copy of the gene. One normal copy of the gene generates enough GAA activity to prevent excess storage of lysosomal glycogen.

Incidence (Frequency)

Pompe disease is very rare. The incidence, or the chance of being born with Pompe disease, is estimated at about one in every forty thousand live births. The estimated frequency of Pompe disease may vary among different ethnic groups and nationalities:

Holland: 1 in 40,000.
(Adults: 1 in 57,000; Infantile: 1 in 138,000)

Southern China and Taiwan: 1 in 50,000 births

African-Americans: 1 in 14,000 births

Caucasian: 1 in 100,000

Assuming a disease frequency of 1 in 40,000 births, the number of people with Pompe disease worldwide is estimated to be somewhere between 5,000 and 10,000 cases.


Pompe disease, like many other LSDs, is a rare disorder. Therefore consultation with specialists that are more familiar with this disease who use qualified laboratories to perform diagnostic tests may expedite the diagnostic process and the implementation of symptom management. Pompe disease diagnosis is usually based on, but not restricted to, the following criteria:

1. Natural history

Progressive generalized muscle weakness (All types)

Heart hypertrophy and macroglossia (Early onset)

Motor developmental delay (Prominent in Early onset) or regression of acquired motor skills (All types)

Previously diagnosed or symptomatic siblings or other relatives

2. Decreased/absent GAA activity in muscle or skin biopsies by qualified laboratories

3. Histopathology: Multivesicular PAS (+) storage in muscle tissue

4. GAA gene mutation(s) in patient’s DNA.

What is Pompe D isease? (po’m-pah or pom-pa’y)

Pompe disease is a rare genetic disorder in which a progressive muscle weakness of all muscles in the body develops as a result of glycogen accumulation or storage in cell vesicles named lysosomes. For this reason, it is considered a Lysosomal Storage Disease or LSD. In unaffected individuals, glycogen in the lysosomes is broken down by acid alpha-glucosidase (GAA), an important and unique lysosomal enzyme that reduces large molecules of glycogen to glucose. Individuals with Pompe disease have very little or no activity of this enzyme because of defects or mutations in the GAA gene.

Onset and Symptoms

There are two major forms of Pompe disease based on age of symptom onset, and on level of enzyme activity:

Early Onset (Infantile)

Symptoms appear shortly after birth and include an enlarged heart and liver and a severe lack of muscle tone

GAA activity in fibroblasts and muscle less than 1% of normal

Most patients die from cardiorespiratory failure or respiratory infection in the first year of life

A non-classical infantile variety is also described in which enzyme activity may be somewhat higher and heart enlargement may be present but is not generally symptomatic

Late Onset (Juvenile and Adult)

Symptoms appear in early-to-late childhood or even much later in life (between 20 to 60 years of age)

GAA activity (average relative to normal). In fibroblasts: Juveniles 4%, Adults 18% (Range 1 – 40%). In muscle: Juveniles 5%, Adults: 8% (Range 3 – 12 %)

Progression of the disease is generally slow, and the primary symptom is muscle weakness in the trunk, lower limbs and diaphragm.

Some adults live their lives without major symptoms or limitations.