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,