latent tuberculosis

Pompe Disease

Priyanka Nair, MD, and Aniruddh Setya, MD

A 10-month-old girl was admitted to the hospital with complaints of fever, cough, and fast breathing for 5 days. It was reported that she had been feeding poorly and had not gained enough weight in the past 5 months. In addition, in the past 6 months, the girl had a history of recurrent chest infections requiring hospitalization, with complaints of increased perspiration, generalized swelling of the body, and suck-rest-suck cycles. 

On physical examination, the infant was tachypneic with chest wall retractions and cyanosis on room air. She appeared emaciated and weighed only 5 kg. Her developmental age corresponded with that of a 5- to 6-month-old infant. The girl had a frog-like posture, a protruding abdomen, and an open mouth. Generalized hypotonia was present, and bilateral lung fields had crepitations with decreased breath sounds in the left lower lobe of her lungs. Hepatomegaly was present, and a chest radiograph revealed cardiomegaly and right upper lobar opacity that were suggestive of infective etiology. 

An electrocardiogram (ECG) was ordered, and results showed shortened PR interval and high voltage QRS complexes (Figure 1). An echocardiogram was also conducted, and results revealed biventricular hypertrophy with severe concentric left ventricular hypertrophy and global hypokinesia. The child was started on antibiotics, decongestive therapy, and supportive treatment, and further investigations were undertaken. Laboratory test results indicated that serum creatinine kinase was 382 U/L (reference range, 25-170 U/L). Aspartate aminotransaminase was 208 U/L (reference range, 8-37 U/L), and alanine transaminase was 127 U/L (reference range, 8-40 U/L). Serum lactate dehydrogenase was 1022 U/L (reference range, 114-480 U/L). Electrolytes, blood sugar, and kidney function tests were normal on multiple occasions. 

Based on the symptoms, signs, and preliminary investigations, a clinical diagnosis of Pompe disease was made. To confirm the diagnosis, a muscle biopsy was taken and sent for histopathologic study, and a blood test for acid maltase activity was conducted. 

By the end of the first week in our care, the girl became afebrile and improved, but oxygen dependence persisted, along with signs of cardiac failure. Angiotensin-converting enzyme inhibitors and diuretics were titrated, and the infant started accepting liquids and semi-solids orally but was unable to swallow solids. Meanwhile, the results of the skeletal muscle biopsy showed small- to large-sized vacuoles replacing most of the sarcoplasm; small groups of atrophic muscle fibers were also seen. Periodic acid–Schiff (PAS) staining showed a variable amount of PAS-positive material in the vacuoles (Figure 2). Acid maltase activity in the patient’s blood by fluorometry was 28 nmol/hr/mg (normal > 60 nmol/hr/mg). The findings were consistent with the clinical diagnosis of Pompe disease. 


Glycogen storage disease type 2, also known as Pompe disease and acid maltase deficiency disease, is an autosomal recessive metabolic disorder caused by mutations of the gene that encodes the enzyme α-1,4 glucosidase (also called acid α glucosidase or acid maltase). This enzyme is needed to break down glycogen and thereby provide energy for the body. A deficiency in acid α glucosidase causes excess amounts of glycogen to accumulate in the lysosomes of cells, impairing the normal function of tissues, especially muscles.1

There are 3 types of Pompe disease: classic infantile-onset, nonclassic infantile-onset, and late-onset. The different forms of the condition are distinguished by their severity and age of onset.2 Our patient had the classic form of infantile-onset Pompe disease, which is seen within a few months of birth. Infants with this disorder typically present with features of congestive heart failure, cardiomegaly, frequent respiratory infections, respiratory distress, hypotonia, developmental delay or loss of acquired motor milestones, failure to thrive, and feeding difficulties. Tongue enlargement and hepatomegaly are variable findings. Without treatment, children with classic infantile-onset of Pompe disease usually die due to heart failure by the age of 1 year.

Physical examination of infants with Pompe disease may reveal sweating, pulsatile precordium, murmur, gallop rhythm, cardiomegaly, decreased breath sounds in the left lower lobe of the lung, signs of respiratory distress, and floppy baby appearance. Macroglossia, open mouth, low facial tone, pooling of oral secretions, and hepatomegaly may also be seen.

Chest roentgenogram will show cardiomegaly, tall QRS complexes and short PR interval on ECG, cardiomyopathy on echocardiography, and a myopathic pattern on nerve conduction velocity/electromyography studies. Elevated creatine phosphokinase, lactate dehydrogenase, serum glutamic-oxaloacetic transaminase, and serum glutamic pyruvic transaminase in blood are usually present. Muscle histochemistry showing increased lysosomal glycogen with vacuolations is characteristic and confirmatory. The vacuoles will stain positive for PAS, as seen in our patient. Reduced activity of acid maltase enzyme activity in dried blood spots, fibroblast, or muscle fiber is gold standard.3

The epidemiologic data on Pompe disease are limited. One study predicted an incidence of 1 in 40,000 for  Pompe disease resulting from acid α glucosidase deficiency and 1 in 138,000 for classic infantile disease after screening blood spots from newborns in the Netherlands for 3 mutant alleles.4 A study by Van den Hout and colleagues5 described 133 cases of infantile Pompe disease, while Kishnani and colleagues6 reported a retrospective chart review of 168 cases of infantile Pompe disease from around the world. 

If the mutation in the family is known, prenatal diagnosis is possible by DNA. If the family does not know of a genetic defect, acid maltase activity can be measured in cultured amniocytes or chorionic villus samples. Early recognition of the clinical characteristics of Pompe disease is important. Diagnosis of Pompe disease is confirmed by biochemical assays that reveal absent or decreased GAA enzyme and enzyme activity in peripheral blood cells, skin fibroblasts, or muscle biopsy. Infants with the condition may present in the first months of life with hypertrophic cardiomyopathy, and the disease rapidly progresses.3


In 2006, the US Food and Drug Administration approved enzyme replacement therapy with recombinant human acid maltase derived from Chinese hamster ovary cells (α-glucosidase, alglucosidase alfa) for use in patients with Pompe disease. Starting enzyme replacement therapy at an early age was linked with positive short-term results such as longer survival without invasive ventilation.7 A study by Chien and colleagues found a link between infants who received a diagnosis after newborn screening with improved cardiac size, muscle pathology, growth, and motor development. Survival was significantly improved compared with untreated historical controls. When compared with treated patients who were diagnosed clinically, survival was improved but not statistically significant.8

Mutational analysis and initiation of enzyme replacement therapy could not be done in our case due to limitation of resources. Most infants with Pompe disease do not survive beyond 6 to 8 months, and approximately 75% to 95% of infants with the condition die from cardiorespiratory failure before 1 year of age.5,6 We explained the grave prognosis to the parents and offered genetic counseling to the family. The infant was sent home on supportive therapy that included diuretics for congestive heart failure, as well as oxygen and β-blockers. It was also requested that the patient return for cardiac function monitoring. Pompe disease should be considered as a possibility in floppy infants presenting with failure to thrive, repeated respiratory infections, and poor feeding. 

Priyanka Nair, MD, is with the Department of Pediatrics at the Indira Gandhi Medical College in Shimla, India.

Aniruddh Setya, MD, is with the Department of Pediatrics at Nassau University Medical Center in East Meadow, New York.


1. Raben N, Plotz P, Byrne BJ. Acid alpha-glucosidase deficiency (glycogenosis type II, Pompe disease). Curr Mol Med. 2002;2(2):145.

2. Library of Medicine. Pompe disease. Accessed September 6, 2016.

3. Bembi B, Cerini E, Danesino C, et al. Diagnosis of glycogenosis type II. Neurology. 2008;71(23 suppl 2):S4-S11.

4. Ausems MG, Verbiest J, Hermans MP, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet. 1999;7(6):713.

5. Van den Hout HM, Hop W, Van Diggelen OP, et al. The natural course of infantile Pompe disease: 20 original cases compared with 133 cases from the literature. Pediatrics. 2003;112(2):332.

6. Kishnani PS, Hwu WL, Mandel H, et al. A retrospective, international, multicenter study on the natural history of infantile onset pompe disease. J Pediatr. 2006;148(5):671.

7. Kishnani PS, Corzo D, Nicolino M, et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68(2):99-109.

8. Chien YH, Lee NC, Thurberg BL, et al. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. 2009;124(6):e1116-e1125.