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.
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.