Pompe disease is caused due to deficiency of acid alpha-glucosidase. The incidence of Pompe,    reported in 1/40,000 patients worldwide, is quite rare. Studies demonstrate patients with Pompe disease show symptoms, such as difficulty in climbing stairs, dyspnea, hypoxia, and pneumothorax. Some Pompe patients present with enlarged esophagus, as observed on X-rays, along with fibrosis and multiple blebs on CT scan. Patients with Pompe disease show emaciation with low body mass index (BMI). In certain cases, they appear extremely thin and cachectic. They may suffer from severe and irreversible respiratory and skeletal muscle destruction. In certain cases, Pompe patients also suffer from frequent pneumothorax due to acceleration of autophagy leading to a self phagocyte of myocyte (type II fiber). It should be noted that pneumothorax is not characteristic of Pompe disease. Late-onset of Pompe Disease is also reported which correlates with prognosis and interval free of therapy.¹

Pompe Disease – Infantile Form

It is considered the most severe form of disease spectrum and referred to as classic infantile Pompe disease. Patients diagnosed with this form of Pompe disease exhibit rapidly progressive disease. It is characterized by weakness, hepatomegaly, prominent cardiomegaly, hypotonia, and death in the first year due to cardiorespiratory failure. Patients may manifest a less severe form of infantile Pompe disease, which is referred to as non-classical infantile Pompe disease. It is characterized by slower progression and less severe cardiomyopathy presenting in the first year of life.²

Pompe Disease – Late-Onset Form

It is an adult-onset form that involves skeletal muscle with slowly progressing myopathy. It typically presents as late as the second or sixth decade of life. Childhood, juvenile, or muscle variant present after infancy. It is classified as a heterogeneous group and does not include severe cardiomyopathy. Occasionally, juvenile-onset can present before 12 months of age. Clinical cases of Pompe disease can show presentations based upon the age of onset. As per studies conducted, the infantile form of Pompe disease has a higher incidence among Chinese and African Americans. The late adult form has a higher incidence in the Netherlands. The incidence of infantile-onset form of Pompe Disease in the Netherlands is 1/183,000. The combined incidence of all forms of Pompe Disease is 1/40,000.²

Pompe Disease – Clinical Features

Pompe disease can be present in infants with severe cardiac manifestations, such as cardiomyopathy, cardiomegaly, arrhythmias, and cardiac failure. It typically presents within the age of 8 and 12 weeks of age with a range from 0 to 12 months. The above-mentioned cardiac manifestations can even lead to arrhythmias and cardiac failure. Other initial signs of Pompe Disease may include respiratory difficulty, muscular weakness, and hypotonia. As per studies conducted, it is seen that most infants require assistant ventilation by 6 months of age, with a median age of death of 8.7 months usually due to respiratory or cardiac failure. As per a study conducted among 169 infants, the overall survival rate was 25.7%, 14.3%, and 9% for 12, 18, and 24 months infants respectively. The ventilator-free survival rate is 16.9%, 8.5%, and 4.9% at 12, 18, and 24 months respectively.³

Prognostic Factors associated with Pompe Disease

Per long-term prognosis of Pompe Disease among infants showed orofacial manifestations in terms of ptosis, hypernasal speech, facial muscle weakness, and hearing loss. Some patients may also require tubes inserted for otitis media with effusion.In terms of the brain, and cognitive function, it showed that some patients had impaired function at the age of 24 months. Some newborns diagnosed with Pompe Disease were found with hypomyelination which resolved before 1 year of age. MRI studies conducted at an older age showed white matter abnormalities. It included T2 weighted hyperintense signals in the white matter and hypomyelination. It also revealed that T-2 weighted hyperintensity increases with time.⁴

Pompe Disease Progression

Pompe Disease can present between the 2nd and 6th decade of life with slow progressing myopathy involving skeletal muscle.⁵ As per studies conducted in infants, prominent heart shadows can be observed in chest X-rays. As per ECG, biventricular hypertrophy can be observed with no abnormalities in the PR interval. The infants showed no signs of cardiac disease at rest, with a normal physical examination. But, thickened ventricular walls and interventricular septum were observed in electromyography. No change was observed in the ejection fraction and PR interval.⁶ 


  1. Kobayashi H, Shimada Y, Ikegami M, et al.  Prognostic factors for the late onset pompe disease with enzyme replacement therapy: from our experience of 4 cases including an autopsy case. Mol Genet Metab. 2010 May;100(1):14-9. doi: 0.1016/j.ymgme.2010.01.015 
  2. 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; Case, Laura [corrected to Case, Laura E]]. Genet Med. 2006;8(5):267-288. doi:10.1097/01.gim.0000218152.87434.f3
  3. Katzin LW, Amato AA. Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy. J Clin Neuromuscul Dis. 2008 Jun;9(4):421-31. doi: 10.1097/CND.0b013e318176dbe4 
  4. Chien YH, Lee NC, Chen CA, et al. Long-term prognosis of patients with infantile-onset pompe disease diagnosed by newborn screening and treated since birth. J Pediatr. 2015 Apr;166(4):985-91.e1-2. doi: 0.1016/j.jpeds.2014.10.068 Epub 2014 Nov 4 
  5. Bhengu L, Davidson A, du Toit P, et al. Lysosomal storage disease medical advisory board, south africa. diagnosis and management of pompe disease. S Afr Med J. 2014 Apr;104(4):273-4. doi:10.7196/samj.7386
  6. Chien YH, Lee NC, Thurberg BL, et al Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. 2009 Dec;124(6):e1116-25. doi: 10.1542/peds.2008-3667

Reviewed by Harshi Dhingra, MD, on 7/27/2021.