Pompe disease is a hereditary multisystemic disorder which occurs due to abnormalities or mutations in the GAA gene. It is a rare disease continuum with varied ages of onset and rates of disease progression. The first symptoms may be seen at any age, from birth to late adulthood. Earlier onset of disease in comparison to later onset commonly shows an association with rapid progression and more severity of disease. Skeletal muscle weakness causing the mobility problems and affecting the respiratory system is seen at all ages.1

The infants who are most severely affected commonly present within the first three months after birth. They suffer from cardiac defects and generalized skeletal muscle weakness with a life expectancy of less than 2 years, if left untreated (classic infantile Pompe disease). Less severe varieties of Pompe disease can have onset during childhood, adolescence, or adulthood. They rarely show cardiac defects, but show a slow progression toward walking disabilities and reduced respiratory function.1

Complications in Infantile Onset Pompe Disease

Infants having Pompe disease have essentially complete or partial GAA activity. They manifest in the first few months of life with eating disorders, poor weight gain, delayed motor milestones and respiratory difficulties with superimposed pulmonary infection. This classical form usually is seen immediately after birth and is represented by hypertrophic cardiomyopathy, cardiorespiratory failure and generalized severe muscle weakness with floppy infant syndrome. The infants usually do not survive beyond the first year of life, if they remain undiagnosed and untreated.2,3 

Generalized Muscle Weakness

Most of the infants have severe generalized muscle weakness. Though the muscles are usually firm to feel, even hypertrophic as well, the infant is not able to hold up his/her head or do a normal movement which leads to head lag and floppiness. Progressive muscle weakness manifests as “floppy baby” appearance.4

Cardiomegaly And Cardiomyopathy 

Many infants suffer from progressive and marked cardiomegaly in the first year of age. Accumulation of glycogen in cardiac muscles results in thickening of the walls of both ventricles and interventricular septum, leading to hypertrophic cardiomyopathy, which can then progress to dilated cardiomyopathy. Rise in left ventricular thickness may also result in left ventricular outflow tract obstruction. The heart autopsy usually shows endocardial fibroelastosis and the size of the heart is increased to 3 times its normal size. 

Electrocardiographic findings depict a shortened PR interval usually seen in association with large QRS complexes. This disease feature may help to differentiate Pompe disease from other etiologies of infant cardiac disease. Cases of atypical infantile form of Pompe disease manifest left ventricular hypertrophy after 6 months of age, however, with absent outflow obstruction, and hence, relatively better cardiac function.5

Respiratory Complications

Respiratory failure is another significant complication apart from cardiac defects. Weakened respiratory muscles and cough reflex are the main concerns for respiratory difficulties and as soon as intubation is done, they immediately develop dependence on the ventilator. Ventilator support or enzyme replacement prolong the patient’s lives but complications linked with other organ systems can manifest.6 Diaphragmatic weakness causes problems in the hygiene of the lower pulmonary segments. Paradoxical respiration referring to diaphragm elevation during inspiration, is noted as well.

Another serious complication is gastrointestinal tract dysfunction including dysphagia, gastro-esophageal reflux, delayed gastric emptying time, and intestinal dysfunction. In cases of difficult swallowing, jejunostomy rather than gastrostomy is required for achieving sufficient feeding without causing aspiration.7

Other System Complications 

The complications in other systems are seen as storage of glycogen occurs throughout the body. A study of 4 cases of infants with Pompe disease showed the patients developed hearing deficits.8 Brain complications can also be observed as excessive storage of glycogen occurs in both glial cells and neurons.9,10 Though reports of recovery in brain myelination after stabilization of the patients have also been noted.7  

Complications In Later Onset Pompe Disease

The non-classical or late onset Pompe disease presents as a milder form than the classical type. Its symptoms manifest at any time after 1 year of age. Involvement of the cardiac system is very rare and symptoms of predominant skeletal muscles involvement are seen. A slow progression of myopathy and respiratory difficulties resulting in varying degrees of disabilities are noted , reducing the average life expectancy. Many of the patients need to use a wheelchair or ventilatory assistance.3 

Muscle Weakness 

Complications of Pompe disease can mimic many musculoskeletal disorders, particularly muscular dystrophies which manifest as limb girdle muscle weakness (LGMW). In Pompe disease, the pelvic muscles are affected more than the shoulder girdle muscles. Scapular winging is usually significant. Flexor muscles in the neck, trunk extensors, and muscles of the abdomen are severely and commonly affected. Involvement of facial muscles along with ptosis (unilateral or bilateral) or dysphagia has also been noted. The phenotypic resemblance with other muscle diseases may cause misdiagnosis or underdiagnosis of Pompe disease.3 

Respiratory Complications

The axial muscle involvement severity in patients of Pompe disease is more common than in other diseases presenting with LGMW and especially unexplained respiratory insufficiency cases point toward Pompe disease.11 In other neuromuscular disorders, respiratory insufficiency is observed after loss of ambulation, whereas, in Pompe disease, they are early clinical manifestations when patients are still ambulant. The various respiratory muscles involved are inspiratory muscles of the chest, diaphragm and the upper airways. Respiratory muscle involvement most frequently leads to early death in these cases. The onset of failure of respiratory muscles can vary from gradual onset to acute onset. The symptoms show an increase with the  progression of disease and include a progressive loss of respiratory muscle function, reduction in vital capacity, sleep disordered breathing, impairment in cough, chronic respiratory insufficiency, and eventually cor pulmonale and acute respiratory failure.3,12


  1. NORD (National Organization for Rare Disorders). 2021. Pompe disease – NORD Accessed July 14, 2021.
  2. van der Ploeg AT, Reuser AJ. Pompe’s disease. Lancet. 2008; 372(9646): 1342-1353. doi:10.1016/S0140-6736(08)61555-X
  3. Manganelli F, Ruggiero L. Clinical features of pompe disease. Acta Myol. 2013;32(2):82-84.
  4. Di Rocco M, Buzzi D, Tarò M. Glycogen storage disease type II: clinical overview. Acta Myol. 2007;26(1):42-44.
  5. Kishnani PS, Howell RR. Pompe disease in infants and children. J Pediatr. 2004;144(5 Suppl):S35-S43. doi:10.1016/j.jpeds.2004.01.053
  6. 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
  7. Chien YH, Hwu WL. A review of treatment of Pompe disease in infants. Biologics. 2007;1(3):195-201.
  8. Van den Hout JM, Kamphoven JH, Winkel LP, et al. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics. 2004;113(5):e448-e457. doi:10.1542/peds.113.5.e448
  9. Gambetti P, DiMauro S, Baker L. Nervous system in Pompe’s disease. Ultrastructure and biochemistry. J Neuropathol Exp Neurol.1971;30(3):412-430. doi:10.1097/00005072-197107000-00008.
  10. Sakurai I, Tosaka A, Mori Y, Imura S, Aoki K. Glycogenosis type II (Pompe). The fourth autopsy case in Japan. Acta Pathol Jpn. 1974;24(6):829-846. doi:10.1111/j.1440-1827.1974.tb00851.x
  11. Alejaldre A, Díaz-Manera J, Ravaglia S, et al. Trunk muscle involvement in late-onset Pompe disease: study of thirty patients. Neuromuscul Disord. 2012;22 Suppl 2:S148-S154. doi:10.1016/j.nmd.2012.05.011
  12. van der Beek NA, de Vries JM, Hagemans ML, et al. Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study. Orphanet J Rare Dis. 2012;7:88. Published 2012 Nov 12. doi:10.1186/1750-1172-7-88

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