Pompe disease is a rare, inherited and usually fatal disease with an incidence of 1 in every 40,000 births.1,2 It occurs due to mutations in the GAA gene that partially or completely eliminate the essential enzyme, acid alpha-glucosidase. The enzyme has a function in intracellular compartments called lysosomes. They function as cellular clearinghouses, ingesting many substances including glycogen, which is normally converted by the GAA into glucose.  Excessive amounts of lysosomal glycogen accumulate throughout the body, but the most seriously affected are the cells of the heart and skeletal muscles.

Up to 300 types of mutations in the GAA gene have been identified tol date. The age of onset and disease severity correlate with the degree of enzyme deficiency. Confirmation of diagnosis of Pompe disease can be done with screening for the common genetic mutations or measurement of the GAA enzyme activity levels in a blood sample. Once diagnosis is made, it is recommended to test all family members in addition to a consultation with a professional geneticist. Identification of carriers can be done by genetic mutation analysis.1

Two Types of Pompe Disease Identified  

Early-Onset, Infantile Form Pompe Disease 

The first description of Classic infantile form was given in 1932 and it characterizes the onset of symptoms soon after birth, generalized muscle weakness, and cardiomegaly in combination with excessive glycogen deposits in almost all organs.2

This form occurs as a result of complete or near-complete GAA deficiency. Symptoms starting in the first few months of life are problems in feeding, poor weight gain, failure to thrive, hypotonia, weakness and floppiness in muscles and very few movements. Marked cardiomegaly and respiratory difficulties in the form of lung infections are observed. Most infants die due to cardiac or respiratory complications before completing the first year of their life. 1,3 

Delay in motor development is observed. Major motor milestones like sitting, rolling over, or standing are not achieved in most cases. On clinical examination, slipping through on vertical suspension and prominent head lag are noted. Tendon reflexes are usually reduced. Most of the infants also show enlarged tongues and moderate enlargement of the liver.

Cardiac ultrasound findings show hypertrophic cardiomyopathy (HCM) with thickening of the ventricular walls and septum. This can lead to outflow tract obstruction and cardiac failure.The electrocardiogram (ECG) findings show high voltages, disturbances in repolarization, and a short PR interval.

Hearing deficits can also be seen as a result of pathological changes in the middle ear, inner ear, and auditory nervous system. This finding had remained unrecognized for a long time as patients had an early death but it must be addressed well if children show a survival longer than expected with enzyme replacement therapy (ERT). This is also applicable for recently noticed osteoporosis and osteopenia in affected cases. The mean age of death in large study groups is found to be 6·0–8·7 months.3

According to the recent review of the natural history of the disease, infantile onset pompe disease (IOPD) shows very fast progression and the time gap between the median age at diagnosis and the median age of first ventilator use was found to be only 1.2 months.4

Late-Onset, Juvenile/Adult Pompe Disease 

The historical names such as ‘childhood’, ‘juvenile’, ‘adult’ glycogenosis type II and acid maltase deficiency were used for less severe forms of Pompe disease.2

It is a heterogeneous type commonly present at a later age than infancy and characteristically excluding severe cardiomyopathy. Adult-onset form is recognized by delayed onset and usually slowly progressive myopathy mainly showing involvement of skeletal muscle that can present as late as the second to sixth decade of life.5 This form occurs due to partial deficiency of GAA.1  

The main symptom is weakness of muscles showing progression to respiratory weakness, and death occurs from respiratory failure after a course lasting for many years. Skeletal muscle dysfunction results in both mobility and respiratory problems. In most of the cases, the heart is uninvolved.1,3 

In a study involving 54 adults, the symptoms analysed were difficulty in sports participation (67%), walking (17%), climbing stairs (28%), rising from an armchair (20%), or rising from a lying position (11%). Other symptoms noted were fatigue (24%) and muscle cramps (17%).6 Patients can have excessive daytime sleepiness, sleep-disordered breathing, and nightly hypoventilation, and they may require non-invasive ventilation.3

A study involving 52 adults showed a marked deterioration in mobility, degree of handicap, and requirement of respiratory support during 2-years follow-up. During this period, 4 out of 52 patients died at a relatively young age (44 years to 68 years), which indicated that the disease is life-threatening not only for infants and children but also for adults.7 

In addition to usual respiratory complications, an aneurysm episode is a potential risk factor which can occur due to accumulation of glycogen in vascular smooth-muscle cells.3


  1. Pompe disease information page.” National Institute of Neurological Disorders and Stroke, US Department of Health and Human Services, www.ninds.nih.gov/Disorders/All-Disorders/Pompe-Disease-Information-Page#disorders-r3.
  2. NORD (National Organization for Rare Disorders). 2021. Pompe disease – NORD (National Organization for Rare Disorders). Accessed July 14 2021.
  3. van der Ploeg AT, Reuser AJ. Pompe’s disease. Lancet. 2008; 372(9646): 1342-1353. doi:10.1016/S0140-6736(08)61555-X
  4. Chien YH, Hwu WL. A review of treatment of Pompe disease in infants. Biologics. 2007;1(3):195-201.
  5. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline [published correction appears in Genet Med. 2006 Jun;8(6):382. ACMG Work Group on Management of Pompe Disease [removed]; Case, Laura [corrected to Case, Laura E]]. Genet Med. 2006;8(5):267-288. doi:10.1097/01.gim.0000218152.87434.f3
  6. 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: 671–77.
  7. Hagemans ML, Hop WJ, Van Doorn PA, Reuser AJ, Van der Ploeg AT. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology 2006; 66: 581–83.

Reviewed by Debjyoti Talukdar, MD, on 7/27/2021.