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A rare metabolic disorder: Pompe's disease.

INTRODUCTION: The disease is named after Joannes Cassianus Pompe, who characterized it in 1932. Pompe disease affects roughly 1 in 100,000 people. (9,10) It has been reported in almost all ethnic populations. As with all cases of autosomal recessive inheritance, children have a 1 in 4 chance of inheriting the disorder when both parents carry the defective gene, and although both parents carry one copy of the defective gene, they are usually not affected by the disorder. (11,12) The severity of symptoms, age at which symptoms begin, and rates of disease progression are related to the degree of alpha-glucosidase deficiency. Prognosis depends on the age of onset on symptoms with a better prognosis being associated with later onset disease. (13)

CASE REPORT: A 4 years old female child born out of second degree consanguiness marraige presented to pediatric opd with progressive lower limb weakness. The child had developmental delay with hypotonia from 6 months of life. In the neonatal period, child presented with repeated respiratory tract infections.

On examination: Upper limbs no hypotonia or contractures; Lower limbs hypotonia was present with involvement of proximal skeletal muscles of the limbs, slight contracture of knee and ankle contracture present. On per abdomen examination hepatomegaly. 4cms below the costal margin was present. Other vitals were within the normal limits. Chest x-ray showed cardiomegaly and Echo revealed cardiomyopathy.


* Serum CPK = 664 microns/ litre (Ref: 25-200 microns/litre)

* Serum LDH = 2550 microns/ litre (Ref: 235-470 microns/litre)

* Alpha- 1,4 glucosidase activity: Ratio = 0.17 (Normal >0.2)

* With Acarbose = 2.6 (Ref: 12.68)

* Without Acarbose = 15.6 (Ref: 25.37-228.6)

* Muscle biopsy = Vacuolar myopathy

* Chest X-Ray = Cardiomegaly

* ECHO-Cardiography = Infiltrative Cardiomyopathy & Left ventricular dysfunction.

PROBABLE CLINICAL DIAGNOSIS: In the view of hypotonia of limbs, developmental delay and cardiomyopathy - Infantile Variant of Pompes disease was considered.

DISCUSSION: Pompe disease, also known as glycogen storage disease type II, is an inherited disorder whose primary symptom is progressive weakness in the muscles used for mobility and breathing. (14,17)

Two forms have been described (18,19):

1. Classic form (Infantile form): It is a severe generalized myopathy and cardiomyopathy. Most commonly affected muscles are cardiac and respiratory muscles along with proximal skeletal muscles of limb. Patients have cardiomegaly, hepatomegaly, and are diffusely hypotonic and weak. Serum CPK levels are greatly elevated. A muscle biopsy of specimen reveals vacuolar myopathy with abnormal lysosomal activities.

2. Late onset form (Juvenile form): It is a much milder myopathy without cardiac or hepatic enlargement.

It may not become clinically expressed until later childhood or early adult life but may be symptomatic as myopathic weakness and hypotonia even in early infancy. Serum CPK levels are greatly elevated and muscle biopsy findings are diagnostic. The diagnosis is confirmed by estimation of acid maltase activity in muscle or liver biopsy.

The usual initial investigations include chest X ray, electrocardiogram and echocardiography. Typical findings are those of an enlarged heart with non-specific conduction defects. Biochemical investigations include serum creatine kinase(typically increased 10 fold) with lesser elevations of the serum aldolase, aspartate transaminase, alanine transaminase and lactic dehydrogenase. Diagnosis is made by estimating the acid alpha glucosidase activity in either skin biopsy (Fibroblasts), muscle biopsy (Muscle cells) or in white blood cells. (20)

In 2006, the FDA approved an enzyme replacement therapy called Myozyme (Alglucosidase alfa, rhGAA), for people with Pompe disease. Myozyme has been shown to decrease heart size, maintain normal heart function, and improve muscle tone and strength in people with the infantile-onset form of the disease. (21) The FDA has approved Myozyme for administration by intravenous infusion of the solution. Myozyme treatment clearly prolongs ventilator-free survival and overall survival. 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. (22,23) Another factor affecting the treatment response is generation of antibodies against the infused enzyme, which is particularly severe in Pompe infants who have complete deficiency of the acid alpha-glucosidase. Immune tolerance therapy to eliminate these antibodies has improved the treatment outcome. (24)

A new treatment option for this disease is called Lumizyme. Lumizyme and Myozyme have the same generic ingredient (Alglucosidase Alfa) and manufacturer (Genzyme Corporation). The difference between these two products is in the manufacturing process. (25) Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease.

The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. (26) Babies born with the infantile-onset form of Pompe disease typically die within the first year of life, though enzyme replacement therapy can now prolong that lifespan. Unfortunately, this disease will greatly curtail the lifespan of those affected. Most people with Pompe disease will die from lung failure. Genetic counseling can provide families with information regarding risk in future pregnancies.


(1.) Pompe, J.C. (1932). "Over idiopathische hypertrophie van het hart". Ned. Tijdschr. Geneeskd. 76: 304-312.

(2.) Trend PS, Wiles CM, Spencer GT, et al; Acid maltase deficiency in adults. Diagnosis and management in five cases. Brain. 1985 Dec; 108( Pt 4): 845-60.

(3.) Brady RO, Schiffmann R; Enzyme-replacement therapy for metabolic storage disorders. Lancet Neurol. 2004 Dec; 3(12): 752-6.

(4.) Coutelle C, Themis M, Waddington SN, et al; Gene therapy progress and prospects: fetal gene therapy-first proofs of concept-some adverse effects; Gene Ther. 2005 Nov; 12(22): 1601-7.

(5.) Messinger, Y.H., et al., Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. Genet Med, 2012. 14(1): p. 135-42.

(6.) Nicolino, M., et al., Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med, 2009. 11(3): p. 210-9.

(7.) Tinkle, B.T. and N. Leslie, Glycogen Storage Disease Type II(Pompe Disease), in GeneReviews, R.A. Pagon, et al., Editors. 1993: Seattle (WA).

(8.) Van der Ploeg, A.T., et al., A randomized study of alglucosidase alfa in late-onset Pompe's disease. N Engl J Med, 2010. 362(15): p. 1396-406.

(9.) Winkel LP, Hagemans ML, van Doorn PA et al. The natural course of non-classic Pompe's disease; a review of 225 published cases. J Neurol 2006 252: 875-84.

(10.) Braunsdorf, WE. Fusiform aneurysm of basilar artery and ectatic internal carotid arteries associated with glycogenosis type 2(Pompe's disease). Neurosurgery. 1987; 21: 748-749

(11.) Pellegrini, N, Laforet, P, Orlikowski, D et al. Respiratory insufficiency and limb muscle weakness in adults with Pompe's disease. Eur Respir J. 2005; 26: 1024-1031

(12.) Reuser, AJJ, Kroos, MA, Hermans, MMP et al. Glycogenosis type II (acid maltase deficiency).Muscle Nerve. 1995; 3: S61-S69.

(13.) Engel, AG, Seybold, ME, Lambert, EH, and Gomez, MR. Acid maltase deficiency: comparison of infantile, childhood, and adult types. Neurology. 1970; 20: 382.

(14.) Ioannou, YA, Zeidner, KM, Friedman, B, and Desnick, RJ. Fabry disease: enzyme replacement therapy in [alpha]-galactosidase A deficient mice. Am J Hum Genet. 1996; 59: A15.

(15.) Ashwell, G and Morell, AG. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol. 1974; 41: 99-128.

(16.) Talsma, MD, Kroos, MA, Visser, G, Kimpen, JL, and Niezen, KE. A rare presentation of childhood pompe disease: cardiac involvement provoked by Epstein-Barr virus infection. Pediatrics. 2002; 109:e65.

(17.) Howell RR, Byrne B, Darras BT, Kishnani P, Nicolino M, van der Ploeg A. Diagnostic challenges for Pompe disease: an under-recognized cause of floppy baby syndrome. Genet Med. 2006 May; 8(5):289-96.

(18.) Zhang, H., Kallwass, H., Young, S.P. et al, Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet Med. 2006; 8: 302-306.

(19.) Mechtler, T.P., Metz, T.F., Muller, H.G. et al, Short-incubation mass spectrometry assay for lysosomal storage disorders in newborn and high-risk population screening. J Chromatogr B Analyt Technol Biomed Life Sci. 2012; 908: 9-17.

(20.) Kumamoto, S., Katafuchi, T., Nakamura, K. et al, High frequency of acid alpha-glucosidase pseudodeficiency complicates newborn screening for glycogen storage disease type II in the Japanese population. Mol Genet Metab. 2009; 97: 190-195.

(21.) Levine, B., Klionsky, D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004; 6:463-477.

(22.) Millington, D.S., Sista, R., Eckhardt, A., Rouse, J., Bali, D., Goldberg, R. et al, Digital microfluidics: a future technology in the newborn screening laboratory?. Semin Perinatol. 2010; 34: 163-169.

(23.) Jones, H.N., Muller, C.W., Lin, M., Banugaria, S.G., Case, L.E., Li, J.S. et al, Oropharyngeal dysphagia in infants and children with infantile Pompe disease. Dysphagia. 2010; 25: 277-283.

(24.) Parenti, G. Treating lysosomal storage diseases with pharmacological chaperones: from concept to clinics. EMBO Mol Med. 2009; 1: 268-279.

(25.) LeBowitz, J.H., Grubb, J.H., Maga, J.A., Schmiel, D.H., Vogler, C., Sly, W.S. Glycosylation-independent targeting enhances enzyme delivery to lysosomes and decreases storage in mucopolysaccharidosis type VII mice. Proc Natl Acad Sci U S A. 2004; 101: 3083-3088.

(26.) Khanna, R., Flanagan, J.J., Feng, J., Soska, R., Frascella, M., Pellegrino, L.J. et al, The pharmacological chaperone AT2220 increases recombinant human acid alpha-glucosidase uptake and glycogen reduction in a mouse model of Pompe disease. PLoS One. 2012; 7: e40776.

Nazeer AhmedJeergal [1], Rizwan-u-zama [2],NaushadAli Malagi [3]

[1] Assistant Professor, Department of Paediatrics, Al Ameen Medical College, Bijapur.

[2] Assistant Professor, Department of Paediatrics, Al Ameen Medical College, Bijapur.

[3] aAssociate Professor, Department of Paediatrics, Al Ameen Medical College, Bijapur.

Financial or Other, Competing Interest: None.

Submission 01-10-2015, Peer Review 03-10-2015, Acceptance 20-10-2015, Published 02-11-2015.

Corresponding Author:

Dr. Nazeer Ahmed Jeergal, Assistant professor, Department of Paediatrics, Al Ameen Medical College, Bijapur.


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Title Annotation:Case Report
Author:Jeergal, Nazeer Ahmed; Rizwan-u-zama; Malagi, Naushad Ali
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Report
Date:Nov 2, 2015
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