Differential Diagnosis

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Infantile-onset Pompe Disease

Differential diagnoses and their features common to infantile-onset Pompe disease are summarised below:1,2

Differential diagnosis Shared symptoms
Acute spinal muscular atrophy 1 (Werdnig-Hoffman disease). Hypotonia, feeding difficulties, progressive proximal muscle weakness, and areflexia; no cardiac involvement.
Endocardial fibroelastosis Respiratory and feeding difficulties, cardiomegaly, and heart failure without significant muscle weakness.
Hypothyroidism Hyotonia and macroglossia.
Myocarditis Cardiomegaly without hypotonia or muscle weakness.
Congenital muscular dystrophy Severe hypotonia and muscle weakness.
Glycogen storage diseases:
Type IIIa (Debrancher deficiency/Cort or Forbes disease)
Type IV (branching enzyme deficiency/Anderson disease)
Cardiomegaly, myopathy, and elevated serum creatine kinase concentration. Liver involvement more dramatic than typically seen in Pompe disease.
Mitochondrial/respiratory chain disorders. Hepatomegaly, muscle weakness, cardiomegaly, and elevated serum creatine kinase concentration.
Absence of hypotonia and presence of cognitive involvement helps to distinguish from Pompe disease.
Danon disease Cardiomegaly, hypertrophic cardiomyopathy, myopathy, and excessive glycogen storage.
Caused by defects in lysosome-associated membrane protein 2.3 Inheritance is X-linked.
Idiopathic hypertrophic cardiomyopathy Biventricular hypertrophy without hypotonia or muscle weakness.
Peroxisomal disorders Hypotonia, hypermegaly.
Carnitine uptake disorder Muscle weakness and cardiomyopathy without elevated serum creatine kinase concentration.

Late-onset Pompe disease

Differential diagnoses and their features common to late-onset Pompe disease are summarised below:1,2,4

Differential diagnosis Shared symptoms
Limb-girdle muscular dystrophy (LGMD) Progressive muscle weakness in the legs, pelvis, and shoulders. Truncal muscles are spared. Elevated serum creatine kinase concentration.
Becker muscular dystrophy (BMD) Progressive proximal muscle weakness, respiratory impairment, difficult walking (prominent quadriceps weakness, calf hypertrophy), and elevated serum creatine kinase concentration.
Primarily affects males and inheritance is X-linked.
Scapuloperoneal syndromes Progressive muscle weakness behind the knees and around the shoulder blades.
Rigid spine syndrome (Selenoprotein N1-related myopathy) Spinal rigidity with lower back pain, respiratory failure, and muscle hypotrophy.
Myasthenia gravis Ptosis, ophthalmoplegia, bulbar dysfunction, proximal muscle weakness, fluctuating course.
Spinal muscular atrophy Progressive proximal muscle weakness and atrophy, respiratory failure, postural tremor, and mild elevated serum creatine kinase concentration.
Polymyositis Progressive, symmetric, unexplained muscle weakness, and elevated serum creatine kinase concentration.
Glycogen storage diseases:
Type IIIa (Debrancher deficiency/Cort or Forbes disease)
Type IV (branching enzyme deficiency/Anderson disease)
Type V (Muscle phosphorylase deficiency/McArdle disease)
Type VII (Muscle phosphofructokinase deficiency/Tauri disease)
Hypotonia, hepatomegaly, muscle weakness with distal involvement, and elevated serum creatine kinase concentration.
Danon disease Cardiomegaly, hypertrophic cardiomyopathy, myopathy, and excessive glycogen storage.
Caused by defects in lysosome-associated membrane protein 2.3 Inheritance is X-linked.
Rheumatoid arthritis Stiffness and pain on exertion
Mitochondrial myopathies Hyptonia, hyporeflexia, hepatomegaly. Some forms with hypertrophic cardiomyopathy, muscle weakness, external ophthalmoplegia, elevated serum creatine kinase concentration.
Lipid storage myopathies Fluctuating muscle weakness with respiratory involvement, sometimes bulbar weakness, elevated serum creatine kinase concentration.

 

References

  1. 1.Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE. Pompe disease diagnosis and management guideline. Genet Med. 2006;8.
  2. 2.Leslie N, Tinkle BT. Glycogen Storage Disease Type II (Pompe Disease). In: Pagon RA, Adam MP, Ardinger HH, al e, editors. GeneReviews® [Internet]. 1993-2015. Seattle (WA): : University of Washington, Seattle; 2013 [Updated 2013]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1261/
  1. 3.Arad M, Maron BJ, Gorham JM, Johnson WH, Saul JP, Perez-Atayde AR. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med. 2005;352.
  2. 4.Al Jasmi F, Al Jumah M, Alqarni F, et al. Diagnosis and treatment of late-onset Pompe disease in the Middle East and North Africa region: consensus recommendations from an expert group. BMC Neurol. 2015;15:1-17.