Glycogen storage disease type II, also referred to as Pompe disease, is an autosomal recessive metabolic disease which damage nerve and muscle cells in the body. It’s caused an accumulation of glycogen from the lysosome because of lack of the lysosomal acid alpha-glucosidase enzyme. It’s the sole glycogen storage disorder using a defect in lysosomal metabolism, and also the very first glycogen storage disorder should be recognized, in 1932 from the Dutch pathologist J. C. Pompe.
The accumulation of glycogen causes progressive muscle fatigue (myopathy) through the body also affects many body cells, especially in the heart, skeletal muscles, liver along with also the nervous system.
Signs and symptoms
The infantile form generally comes to medical care within the first month or two of life. The typical presenting attributes are cardiomegaly (92 percent), hypotonia (88 percent), cardiomyopathy (88 percent), respiratory distress (78 percent), muscle fatigue (63 percent), feeding problems (57 percent) and also failure to flourish (50 percent).
The key clinical trials incorporate floppy baby look, delayed motor milestones and feeding problems. Moderate hepatomegaly can be present. Facial features include macroglossia, wide open mouth, wide open eyes, nasal flaring (because of respiratory distress), and inferior facial muscle tone. Cardiopulmonary participation is illustrated by increased respiratory rate, use of accessory muscles for respiration, recurrent chest infections, decreased air entry at the left lower zone (because of cardiomegaly), arrhythmias and signs of heart failure.
Cause of glycogen storage disease
This usually means the faulty gene is situated on an autosome, and 2 copies of the gene–one from each parent–are all needed to be born with the disease. Like all cases of autosomal recessive inheritance, kids have a 1 in 4 chance of inheriting the disease when both parents carry the faulty gene, and even though both parents carry a single copy of the faulty gene, they’re generally not impacted by the disease.
The disease is caused by a mutation at a gene (acid alpha-glucosidase: also called acid maltase) on the long arm of chromosome 17 in 17q25.2-q25.3 (base group 75,689,876 into 75,708,272). The amount of mutations explained is now (in 2010) 289 using 67 being non-pathogenic mutations and 197 pathogenic mutations. The rest continue to be assessed for their association with illness.
The gene spans approximately 20 kb and comprises 20 exons together with the initial exon being noncoding. The coding sequence of this putative catalytic site domain name is interrupted in the middle by an intron of 101 bp. The promoter has attributes characteristic of a ‘housekeeping’ gene. The GC content is large (80 percent) and different TATA and CCAAT motifs are missing.
Treatment of glycogen storage disease
Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease. Genetic counseling can provide families with information regarding risk in future pregnancies.
A new treatment option for this disease is called Lumizyme. Lumizyme and Myozyme have the same generic ingredient (Alglucosidase Alfa) and manufacturer (Genzyme Corporation). The difference between these two products is in the manufacturing process. Today, the Myozyme is made using a 160-L bioreactor, while the Lumizyme uses a 4000-L bioreactor. Because of the difference in the manufacturing process, the FDA claims that the two products are biologically different. Moreover, Lumizyme is FDA approved as replacement therapy for late-onset (noninfantile) Pompe disease without evidence of cardiac hypertrophy in patients 8 years and older. Myozyme is FDA approved for replacement therapy for infantile-onset Pompe disease.
Recent studies on chaperone molecules to be used with Myozyme are starting to show promising results on animal models.
