Glycogenoses (glycogen storage diseases)

Pompe disease:

Synonyms:

a.k.a. type 2 glycogenosis a.k.a. glycogen storage disease type II GSD II a.k.a. acid maltase deficiency, rare:

Diagnosis:

A type of lysosomal storage disease and a glycogen storage disease.

Genetics:

GAA gene chr. 17. Protein= alpha glucosidase
Autosomal recessive

Biochemical assay:

Confirms the diagnosis.
Enzyme activity: reduced
Skin fibroblasts are best
Muscle biopsy: Decreased activity of acid maltase, but normal neutral maltase

Clinical features:

Wide spectrum. Usually fixed weakness. Proximal muscle weakness. Axial muscle weakness. Respiratory muscle weakness.
Pompe disease= infant with massive cardiomyopathy +hypotonia

Muscle biopsy:

HandE: Vacuoles. GMT: vacuolations, mitochondrial change. PAS: positive vacuoles. Acid phosphatase: stained vacuoles
Electron microscopy: lysosomal glycogen lakes

Findings on investigations:

EMG:

  • Myopathic picture in limbs: increased insertional activity, irritation, fibrillation potentials.
  • Myotonic discharges in paraspinal muscles

CK: modestly raised, normal

Treatment:

Enzyme replacement therapy ERT:

  • Acid a-glucosidase 20 mg/kg I.V. every 2 weeks
  • For all infants
  • Consider in adults

 

Forbes disease a.k.a. type 3 glycogenosis

Muscle biopsy:

Electron microscopy: cytoplasmic storage
Amylo-1,6 glucosidase deficiency
 

McArdle disease:

Synonyms:

a.k.a. type 5 glycogenosis a.k.a. myophosphorylase deficiency MPH deficiency:

Diagnosis:

Biochemical assay confirms the diagnosis

Clinical features:

Exercise intolerance, exercise induced cramps and exercise induced Myoglobinuria
Fixed weakness (proximal) may occur
Second wind phenomenon occurs
Renal failure may occur

Muscle biopsy:

Subtle findings
HandE: sometimes shows subsarcolemmal vacuoles. Necrosis may occur in myoglobinuric phase. PAS: positive vacuoles. Acid phosphatase: negative vacuoles
Electron microscopy: cytoplasmic storage of glycogen i.e. nonlysosomal. But this is nonspecific
Myophosphorylase stain: Negative phosphorylase reaction confirms the diagnosis, positive staining in blood vessels (internal control)

Findings on investigations:

EMG:

  • Electrical silence during a cramp
Genetics:

Autosomal recessive. PYGM gene chr. 11q13
 

Tarui disease:

Synonyms:

a.k.a. type 7 glycogenosis a.k.a. phosphofructokinase deficiency PFKM deficiency

Clinical features:

Broad: exercise intolerance, cramps. Fixed weakness
Moderate hemolytic anemia, gout

Muscle biopsy:

Electron microscopy: cytoplasmic storage
Normal phosphorylase reaction
PFK Muscle isoform: absent staining
PFKM gene mutation chr. 12q13.3, PFK Muscle isoform

Findings on investigations:

CK, bilirubin, uric acid, reticulocytes: increased
 

Type 8 glycogenosis

Synonyms:

a.k.a. phosphorylase kinase deficiency PHK deficiency

Clinical features:

Broad: exercise intolerance, cramps
PHKA gene mutation chr. Xp22.2,
 

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