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Mutations in the GAA gene have been found to be associ-
ated with GLYCOGEN STORAGE DISEASE II; GSD2
(OMIM #232300), is an autosomal recessive lysosomal
storage disease. Pompe disease has been classified into:
classic infantile, juvenile and adult forms involvement of
skeletal muscles dominates the clinical picture Matsuishi et
Classic infantile-onset: Age of onset is usually in the first two to six months of life, with hypotonia and muscle weak- ness, motor developmental delay, feeding difficulties, fail- ure to thrive, respiratory distress or infections, cardiac prob- lems (cardiomegaly, generalised hypertrophy, a murmur and cardiomyopathy) and hepatomegaly. Children with this form usually have a severe deficiency of the acid alpha-glu- cosidase enzyme. If not treated, the symptoms progress rapidly and the hypertrophic cardiomyopathy may develop a left ventricular outflow tract obstruction or compress adja- cent respiratory structures. Cardiorespiratory failure could result in death within the first year of life.compress adjacent respiratory structures. Cardiorespiratory failure could result in death within the first year of life.
INon Classic infantile-onset: Age of onset is within the first
year of life, with motor developmental delay and weakness.
Cardiomegaly is less common, and cardiac involvement is
not present in all the patients. The rate of clinical progression
is slower and without treatment, death will usually occur in
childhood as a result of respiratory insufficiency.
Late or adult onset form: The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence or adulthood. Late-onset Pompe disease is usually milder than infantile-onset and is less likely to in- volve the heart. Clinical features include proximal muscle weakness, fatigue, orthopnoea, sleep apnea and respira- tory failure. Individuals affected by late-onset have a par- tial deficiency (2-40%) of the enzyme acid alpha-glucosi- dase. Without treatment, morbidity and mortality occur mainly as a result of respiratory insufficiency and failure, with death occurring anytime from the third decade on- wards mainly as a result of respiratory insufficiency and fail- ure, with death occurring anytime from the third decade on- wards.
Patient born of 3° consanguineous marriage presented with peripheral hypotonia with quadriparesis, hypertrophic car- diomyopathy, and has been evaluated for glycogen storage pompe disease type II.
|Test Name||Sample Type||Method||Description|
|Enzyme analysis for Alpha glucosidase||2-4 ml sodium heparin blood||Fluorometry assay with artificial substrate||Assay carried on leukocytes|
|Clinical Exome Sequencing||2-4 ml EDTA blood||Next Generation Sequencing||Mean coverage of 80-100X coverage. Target coverage 200X|
In such type of carrier status cases, Validation of the variant by Sanger sequencing and/or Parental segregation analysis can be recommended.