It was first identified in 1932 by Dutch pathologist Joannes Cassianus Pompe, making it the first glycogen storage disease to be discovered.

The usual presenting features are cardiomyopathy, cardiomegaly, hypotonia, respiratory distress, muscle weakness, feeding difficulties, and failure to thrive.

[2][citation needed] IOPD patients can be further classified by Cross-Reactive Immunological Material (CRIM) status which is an important predictor of clinical response.

The main clinical findings include floppy baby appearance, delayed motor milestones, and feeding difficulties.

Cardiopulmonary involvement is manifested by increased respiratory rate, use of accessory muscles for respiration, recurrent chest infections, decreased air entry in the left lower zone (due to cardiomegaly), arrhythmias, and evidence of heart failure.

[citation needed] Before the development of a treatment, the median age at death in untreated cases was 8.7 months, usually due to cardiorespiratory failure.

[citation needed] Late-onset features include impaired cough, recurrent chest infections, hypotonia, progressive muscle weakness, delayed motor milestones, difficulty swallowing or chewing, and reduced vital capacity.

In the early-onset form, an infant will present with poor feeding causing failure to thrive, or with difficulty breathing.

[citation needed] In the late-onset form, an adult will present with gradually progressive arm and leg weakness, with worsening respiratory function.

[5] The infantile-onset form is usually diagnosed at 4–8 months; muscles appear normal but are limp and weak preventing the child from lifting their head or rolling over.

[medical citation needed] On April 28, 2006, the US Food and Drug Administration (FDA) approved a biologic license application (BLA) for alglucosidase alfa, rhGAA (Myozyme),[6][7] the first treatment for patients with Pompe disease, developed by a team of Duke University researchers.

This was based on enzyme replacement therapy using biologically active recombinant human alglucosidase alfa produced in Chinese Hamster Ovary cells.

[8] The safety and efficacy of Myozyme were assessed in two separate clinical trials in 39 infantile-onset patients with Pompe disease ranging in age from 1 month to 3.5 years at the time of the first infusion.

The treatment is not without side effects which include fever, flushing, skin rash, increased heart rate, and even shock; these conditions, however, are usually manageable.

[citation needed] Myozyme costs an average of US$300,000 a year and must be taken for the patient's entire life, so some American health insurers have refused to pay for it.

Their recommendation was to provide funding to treat a tiny subset of Pompe patients (Infants less one year of age with cardiomyopathy).

[medical citation needed] Myozyme is FDA approved for replacement therapy for infantile-onset Pompe disease.

In a study[23] which included the largest cohort of patients with Pompe disease treated with enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment clearly prolongs ventilator-free survival and overall survival in patients with infantile-onset Pompe disease as compared to an untreated historical control population.

Furthermore, the study demonstrated that initiation of ERT before six months of age, which could be facilitated by newborn screening, shows great promise to reduce the mortality and disability associated with this devastating disorder.

[24] Another factor affecting the treatment response is the generation of antibodies against the infused enzyme, which is particularly severe in Pompe infants who have a complete deficiency of the acid alpha-glucosidase.

[27] The study was undertaken to evaluate the safety and efficacy of aglucosidase alfa in juvenile and adult patients with Pompe disease.

LOTS was a randomized, double-blind, placebo-controlled study that enrolled 90 patients at eight primary sites in the United States and Europe.

The primary efficacy endpoints of the study sought to determine the effect of Myozyme on functional endurance as measured by the six-minute walk test and to determine the effect of aglucosidase alfa on pulmonary function as measured by percent predicted forced vital capacity.

The basis for the disease remained a puzzle until Christian de Duve's discovery of lysosomes in 1955 for which he won the Nobel Prize in 1974.

His co-worker Henri G. Hers realised in 1965 that the deficiency of a lysosomal enzyme (alpha-glucosidase) for the breakdown of glycogen could explain the symptoms of Pompe disease.

In the early 1990s Dutch scientists Arnold Reuser and Ans van der Ploeg were able to show that using alpha-glucosidase containing phosphorylated mannose residues purified from bovine testes increased the enzyme's activity in normal mouse muscles.

[34] This work eventually culminated in the start of clinical trials with the first clinical trial including four babies receiving enzyme from rabbit milk at Erasmus MC Sophia Children's Hospital and three babies receiving enzyme grown in CHO cells[25] at Duke University in 1999.

Genzyme first partnered with Pharming Group NV which had managed to produce acid alpha-glucosidase from the milk of transgenic rabbits.

In November 2001, Genzyme chief executive Henri Termeer organised a systematic comparison of the various potential drugs in a mouse model of Pompe disease.

In 2021, in-utero enzyme replacement therapy infusions were provided to the fetus of an Ottawa, Ontario, mother who had had two previous children with Pompe disease.