SCIENTIFIC BACKGROUND

GAA

SCIENTIFIC BACKGROUND

Pompe disease (or glycogenosis type II) is an autosomal recessive inherited disease and belongs to the group of lysosomal glycogen storage diseases. A reduced activity of the enzyme 1,4-α-glucosidase (GAA, acid maltase) leads to a dysfunction of glycogen degradation in the lysosomes. The disease is caused by pathogenic variants in the GAA gene.

 

The enzyme defect leads to a progressive systemic accumulation of glycogen in the lysosomes. Heart cells and type II muscle cells are predominantly affected. Pompe disease is classified into two forms based on the occurrence of the first symptoms of the disease:

 

  • In the infantile course, there is a homogeneous clinical picture with marked muscle weakness ("floppy infants"), respiratory insufficiency and developmental delay. If untreated, most children die of heart failure within the first year of life.
  • In the late-onset form with a highly variable course, differentiation from other muscle diseases is difficult. Symptoms may include progressive muscle weakness, especially of the muscles close to the trunk, back pain, scoliosis, dyspnea, sleep apnea, morning headaches, and daytime fatigue.

 

Molecular genetic testing of the GAA gene should be performed before enzyme activity determination of 1,4-α-glucosidase. The disease is inherited in an autosomal recessive pattern, meaning that both alleles must be affected for the enzyme deficiency to manifest clinically. It is a rare disease with a worldwide prevalence of approximately 1:40,000. In addition to symptomatic treatment, enzyme replacement therapy has been available in Europe since 2006.

 

References

Tarnopolsky et al. 2016, Can J Neurol Sci 43:472-85 / ACMG Practice Guideline, Wang et al. 2011, Genetics In Medicine 13:457 / Parkinson-Lawrence et al. 2010, Physiology, 25:102 / Schoser 2007, Akt Neurol 34:283 / ACMG Practice Guideline, Kishnani et al. 2006, Genetics IN Medicine 8:267 / Vellodi 2004, Brit J of Haematology, 128:413

GENES

GAA

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Exciting news in genetic research! The Human Pangenome Reference Consortium has unveiled an improved version of the human pangenome reference. This c...

Read more

Duchenne muscular dystrophy, a rare inherited muscle disorder characterized by progressive muscle weakness and degeneration that leads to difficultie...

Read more

May 12 is International Nurses Day. It is celebrated on Florence Nightingale’s birthday. She pioneered the field of modern nursing through her dedi...

Read more

Hair loss is a common problem that affects millions of men and women around the world. While genetics is believed to be the most significant factor c...

Read more

Depression is a serious mental health issue affecting over 280 million people worldwide. Recent research has revealed a potential link between gut he...

Read more

If you are unlucky enough to suffer from migraines, you will know that a migraine is not just a bad headache. The headache and accompanying symptoms ...

Read more

Autism spectrum disorder (ASD) is a neurological developmental disorder that affects brain development and function. This affects how people learn, b...

Read more

Researchers have developed a method called "Mendelian Phenotype Search Engine" (MPSE) to identify which sick infants in the neonatal intensive care u...

Read more

Did you know that wisdom teeth are actually an evolutionary leftover from our ancient ancestors that no longer serve their original purpose? These mo...

Read more

Azoospermia is a medical condition characterized by the absence of sperm in the ejaculate and is a major cause of male infertility. It affects 1 in 1...

Read more