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glycogen storage disease type-II (Pompe type glycogen storage disease, infantile acid maltase deficiency)
Adult, juvenile & infant types.
Epidemiology:
1) rare genetic disorder
2) 1 in 40,000 births
Pathology:
1) deficiency in alpha-1,4-glucosidase (GAA)
2) build-up of glycogen
3) affects heart, skeletal muscles, liver, & nervous system
Genetics:
1) autosomal recessive inheritance
2) defects in alpha-1,4-glucosidase gene
Clinical manifestations:
progressive muscle weakness
3 forms defined by age of onset & progression of symptoms
1) infantile, or early onset, noticed shortly after birth
a) severe hypotonia, muscle weakness, hepatomegaly, cardiomegaly
b) mental function is not affected
c) dysphagia
d) tongue may protrude and become enlarged
e) development appears normal for the first weeks or months but slowly declines as the disease progresses
f) most children die from respiratory or cardiac complications before 2 years of age
2) juvenile onset symptoms appear in early to late childhood
a) progressive weakness of respiratory muscles in the trunk, diaphragm
b) lower limb weakness
c) exercise intolerance
d) intelligence is normal
e) most patients do not live beyond the 2nd or 3rd decade of life
3) adult onset
a) generalized muscle weakness
- proximal muscle weakness
- difficulty in climbing stairs
b) wasting of respiratory muscles in the trunk & diaphragm
c) respiratory distress
d) headache at night or upon waking
e) diminished deep tendon reflexes
f) intellect is not affected
g) a small number of adult patients live without major symptoms or limitations
Laboratory:
- GAA gene mutation
Special laboratory:
-> normal response of plasma glucose to IM glucagon
Management:
1) alglucosidase alfa (Myozyme, Lumizyme) or avalglucosidase alfa-ngpt (Nexviazyme)
- cipaglucosidase alfa-atga (Pombiliti) + miglustat (Opfolda) for adult type
2) cardiac & respiratory complications are treated symptomatically
3) physical therapy
4) occupational therapy
5) changes in diet may provide temporary improvement but will not alter the course of the disease
6) genetic counseling
7) prognosis
a) varies according to the onset and severity of symptoms
b) particularly lethal in infants & young children
Related
lysosomal alpha-glucosidase; alpha-1,4-glucosidase; acid alpha glucosidase; acid maltase (GAA)
General
glycogen storage disease (glycogenosis)
Properties
DEFICIENT-PROTEIN: lysosomal alpha-glucosidase
COMPARTMENT: lysosome
MOTIF: signal sequence {1-27}
P-TYPE {81-130}
MOTIF: cysteine residue {C82}
MODIFICATION: cysteine residue {C109}
cysteine residue {C92}
MODIFICATION: cysteine residue {C108}
cysteine residue {C103}
MODIFICATION: cysteine residue {C127}
cysteine residue {C108}
MODIFICATION: cysteine residue {C92}
cysteine residue {C109}
MODIFICATION: cysteine residue {C82}
cysteine residue {C127}
MODIFICATION: cysteine residue {C103}
N-glycosylation site {N140}
N-glycosylation site {N233}
N-glycosylation site {N390}
N-glycosylation site {N470}
aspartate residue {D518}
glutamate residue {E521}
N-glycosylation site {N652}
N-glycosylation site {N882}
N-glycosylation site {N925}
Database Correlations
OMIM 300257
References
- Clinical Diagnosis & Management by Laboratory Methods,
J.B. Henry (ed), W.B. Saunders Co., Philadelphia,
PA. 1991, pg 185
- NINDS Pompe Disease Information Page
https://www.ninds.nih.gov/Disorders/All-Disorders/Pompe-Disease-Information-Page