Differential Diagnosis

The ability to correctly differentiate Pompe disease from other disorders is crucial for minimizing diagnostic delays and optimizing patient outcomes. However, because Pompe disease is rare and many of its signs and symptoms are shared with other medical conditions the differential diagnosis can be challenging.

Pompe disease should be considered when signs and symptoms suggest progressive muscular degeneration, especially of the proximal limb-girdle muscles and respiratory muscles, as well as cardiomegaly/cardiomyopathy in infants. Once a clinical suspicion is raised, Pompe disease can be tested for by measuring GAA enzyme activity. 

Learn more about testing for Pompe disease

The symptoms of Pompe disease are similar to those of the diseases below and Pompe disease should be considered as part of any differential diagnosis.

See more details on Pompe disease signs and symptoms in infants

Potential differential diagnosis for Infants

Differential Diagnoses Shared Signs & Symptoms

Spinal muscular atrophy I (Acute Werdnig-Hoffman disease)

Hypotonia

Progressive proximal muscle weakness

Absent reflexes

Feeding difficulties

Elevated creatine kinase (CK)

Hypothyroidism

Hypotonia

Macroglossia

Congenital muscular dystrophy

Hypotonia (severe)

Muscle weakness

Danon disease

Hypertrophic cardiomyopathy

Skeletal muscle myopathy

Vacuolar glycogen storage

Elevated CK

Endocardial fibroelastosis

Breathlessness

Feeding difficulties

Cardiomegaly

Heart failure

Carnitine deficiency

Cardiomyopathy

Muscle weakness

Glycogen storage diseases (GSD) III & IV

Hepatomegaly

Hypotonia

Cardiomegaly

Muscle weakness

Elevated CK

Idiopathic hypertrophic cardiomyopathy

Biventricular hypertrophy

Myocarditis

Cardiomegaly

Mitochondrial/respiratory chain disorders

Hepatomegaly

Cardiomyopathy

Myopathy

Elevated CK

Peroxisomal disorders

Hypotonia

Hepatomegaly

Potential differential diagnoses for Children & Adults

Children and adults with Pompe disease often have a non-specific presentation, which makes Pompe difficult to distinguish from other conditions, such as various muscular dystrophies. The symptoms of Pompe disease are similar to those of the diseases below and Pompe disease should be considered as part of any differential diagnosis.[1-3], [5], [6]

See more details on Pompe disease signs and symptoms in children and adults

Differential Diagnoses Shared Signs & Symptoms

Limb girdle muscular dystrophy (LGMD)

Progressive muscle weakness - in hips, legs, or shoulders

Abnormal gait

Elevated creatine kinase (CK)

Becker/Duchenne muscular dystrophy

Progressive muscle weakness - proximal

Respiratory impairment

Difficulty walking

Elevated CK

Polymyositis

Progressive muscle weakness - often symmetrical

Difficulty swallowing

Elevated CK

Mitochondrial myopathies

Hypotonia

Hyporeflexia

Hepatomegaly

Exercise intolerance (in some forms)

Muscle weakness (in some forms)

Headache (in some forms)

Breathlessness (in some forms)

Elevated CK (in some forms)

Carnitine deficiency

Muscle weakness - in hips, shoulders, & upper arms & legs

Glycogen storage diseases III & IV

Hypotonia

Hepatomegaly

Muscle weakness

Elevated CK

Glycogen storage disease V

Elevated CK

Muscle cramps during exercise

Exercise intolerance

Danon disease

Skeletal muscle myopathy

Muscle weakness - proximal

Elevated CK

Rheumatoid arthritis

Generalized weakness

Stiffness

Fatigue

Musculoskeletal symptoms

Spinal muscular atrophy

Atrophy of voluntary muscles

Elevated CK

Kennedy’s disease

Difficulty breathing

Difficulty swallowing

Elevated CK

Amyotrophic lateral sclerosis (ALS)

Progressive muscle weakness

Respiratory impairment

Elevated CK

References

  1. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med 2006; 8:267-88.
  2. Gilbert-Barness E. Review: Metabolic cardiomyopathy and conduction system defects in children. Ann Clin Lab Sci 2004; 34:15-34.
  3. Roe CR, Ding J. Mitochondrial Fatty Acid Oxidation Disorders. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. New York, New York: McGraw-Hill; 2001.
  4. 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 2006:8;1-8.
  5. Gilchrist JM. Overview of neuromuscular disorders affecting respiratory function. Semin Respir Crit Care Med 2002; 23:191-200.
  6. Andres PL, Thibodeau LM, Finison LJ, Munsat TL. Quantitative assessment of neuromuscular deficit in ALS. Neurol Clin 1987; 5:125-41.

Find Diagnostic Labs

Get a list of laboratories that can perform enzyme assays and other useful tests to aid in the diagnosis of Pompe disease.

Download Lab List 
(Intended for the U.S. only)

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