Glycogen storage disease type II (also called Pompe disease or acid maltase deficiency) is a rare, autosomal recessive metabolic disorder caused by a deficiency in the enzyme acid maltase (EC 3.2.1.20), which is needed to break down glycogen, a stored form of sugar used for energy. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings E00-E35 - Endocrine diseases (E00-E07 Thyroid gland / Thyroid hormone ( Congenital iodine-deficiency syndrome ( The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Inborn errors of metabolism comprise a large class of genetic Diseases involving disorders of Metabolism. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Maltase ( (acid maltase alpha-14-glucosidase is an Enzyme produced by the cells lining the Small intestine that breaks down the Disaccharide Maltose This article is about the Enzyme Commission codes For the European Commission system for coding chemicals see EC-No. Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells Sugar is a class of edible Crystalline substances mainly Sucrose, Lactose, and Fructose. It is the only glycogen storage disease with a defect in lysosomal metabolism, and was the first glycogen storage disease to be identified, in 1932. Glycogen storage disease (synonyms glycogenosis, dextrinosis) is any one of several inborn errors of metabolism that result from Enzyme defects Glycogen storage disease (synonyms glycogenosis, dextrinosis) is any one of several inborn errors of metabolism that result from Enzyme defects Year 1932 ( MCMXXXII) was a Leap year starting on Friday of the Gregorian calendar.

The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system. In Medicine, a myopathy is a neuromuscular Disease in which the Muscle fibers do not function for any one of many reasons resulting in Muscular weakness The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic Skeletal muscle is a type of Striated muscle, which usually attaches to tendons The liver is a vital organ in the human body and is present in Vertebrates and some other animals The nervous system is a Network of specialized cells that communicate information about an animal's surroundings and itself

Genetic prevalence

Glycogen storage disease type II has an autosomal recessive pattern of inheritance.

The disorder is estimated to occur in about 1 in 40,000-300,000 births.

It has an autosomal recessive inheritance pattern. This means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are required to be born with the disorder. An autosome is a non-sex Chromosome. It is an ordinarily paired type of chromosome that is the same in both Sexes of a species. As with all cases of autosomal recessive inheritance, children have a 1 in 4 chance of inheriting the disorder when both parents carry the defective gene, and although both parents carry one copy of the defective gene, they are usually not affected by the disorder.

Variants

Pompe disease has historically been divided into three forms defined by age of onset and progression of symptoms (see below). More recently there has been a trend to divide the disease into two groups: infantile onset (involving the massive enlargement of the heart) and late onset (no heart enlargement):

Infantile, or early onset, is noticed shortly after birth. Childbirth (also called labour, birth, partus or parturition) is the culmination of a Human Pregnancy or Symptoms include severe lack of muscle tone, weakness, and enlarged liver and heart. Mental function is not affected. Development appears normal for the first weeks or months but slowly declines as the disease progresses. Swallowing may become difficult and the tongue may protrude and become enlarged. The tongue is the large bundle of Skeletal muscles on the floor of the Mouth that manipulates Food for chewing and swallowing (deglutition Most children die from respiratory or cardiac complications before 2 years of age.

Juvenile onset symptoms appear in early to late childhood and include progressive weakness of respiratory muscles in the trunk, diaphragm and lower limbs, as well as exercise intolerance. For other types of diaphragm see Diaphragm. In the Anatomy of Mammals the thoracic diaphragm is a sheet of Muscle Intelligence is normal. Intelligence (also called intellect) is an Umbrella term used to describe a property of the Mind that encompasses many related abilities such as the capacities

Adult onset symptoms also involve generalized muscle weakness and wasting of respiratory muscles in the trunk, lower limbs, and diaphragm. Many patients report respiratory distress, headache at night or upon waking, diminished deep tendon reflexes, and proximal muscle weakness, such as difficulty in climbing stairs. Intellect is not affected. A small number of adult patients live without major symptoms or limitations

Pompe's disease is one of the infiltrative causes of restrictive cardiomyopathy.

Treatment

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.

On April 28, 2006 the US Food and Drug Administration approved a biologics license application (BLA) for Myozyme (alglucosidase alfa, rhGAA), the first treatment for patients with Pompe disease primarily developed by Dr. Alglucosidase alfa ( Myozyme, Genzyme) is an Enzyme replacement therapy (ERT Orphan drug for treatment of Pompe disease ( Glycogen storage Yuan-Tsong Chen (陳垣崇) while he was at Duke University (Dr. Duke University is a private Research University located in Durham, North Carolina, United States. Chen is currently the director of the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan). The Academia Sinica ( "Chinese Academy" in Latin) headquartered in the Nangang District of Taipei, is the National academy Taipei ( Taiwanese Pe̍h-ōe-jī: Tâi-pak-chhī Jhuyin Fuhao: ㄊㄞˊ ㄅㄟˇ ㄕˋ Hakka: Thòi-pet-sṳ has been the capital of Taiwan ( Taiwanese: Tâi-oân/Tāi-oân (historically 大灣/台員/大員/台圓/大圓/台窩灣 is an Island in East Asia. Myozyme falls under the FDA Orphan Drug designation and was approved under a priority review. In the US, an orphan drug is any drug developed under the Orphan Drug Act of January 1983 ("ODA" a Federal law concerning Rare diseases Myozyme is manufactured by Genzyme Corp. in Cambridge, MA, USA. FDA Approval News for Myozyme

The FDA approved Myozyme for administration by intravenous infusion of solution into a vein. The safety and efficacy of Myozyme were assessed in two separate clinical trials in 39 infantile-onset patients with Pompe disease ranging in age from 1 month to 3. 5 years at the time of the first infusion.

Myozyme costs an average of $300,000 a year, and must be taken for the patients' entire life. Some insurers have refused to pay for it. ^[1]

On August 14, 2006, Health Canada approved Myozyme for the treatment of Pompe disease. On June 14, 2007 the Canadian Common Drug Review issued their recommendations regarding public funding for Myozyme therapy. Their recommendation was to provide funding to treat a very small subset of Pompe patients (Infants less one year of age with Cardiomyopathy). ^[2] The vast majority of developed countries are providing access to therapy for all diagnosed Pompe patients. ^[3]

Prognosis

The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. Without treatment the disease is particularly lethal in infants and young children.

Myozyme (alglucosidase alfa), a recombinant form of the human enzyme acid alpha-glucosidase, is currently being used to replace the missing enzyme. Myozyme helps break down glycogen. In a study^[4] which included the largest cohort of patients with Pompe disease treated with enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment clearly prolongs ventilator-free survival and overall survival in patients with infantile-onset Pompe disease as compared to an untreated historical control population. Furthermore, the study demonstrated that initiation of ERT prior to 6 months of age, which could be facilitated by newborn screening, shows great promise to reduce the mortality and disability associated with this devastating disorder.

On December 13, 2007, Genzyme released the initial results of its Late Onset Treatment Study (LOTS). The study was undertaken to evaluate the safety and efficacy of Myozyme in juvenile and adult patients with Pompe disease. LOTS was a randomized, double-blind, placebo-controlled study that enrolled 90 patients at eight primary sites in the United States and Europe. Participants received either Myozyme or a placebo every other week for 18 months. The average age of study participants was 44 years. The primary efficacy endpoints of the study sought to determine the effect of Myozyme on functional endurance as measured by the six-minute walk test and to determine the effect of Myozyme on pulmonary function as measured by percent predicted forced vital capacity.

The results showed that, at 18 months, patients treated with Myozyme increased their distance walked in six minutes by an average of approximately 30 meters as compared with the placebo group (P=0. 0283; Wilcoxon test). The placebo group did not show any improvement from baseline. The average baseline distance walked in six minutes in both groups was approximately 325 meters. Percent predicted forced vital capacity in the group of patients treated with Myozyme increased by 1 percent at 18 months. In contrast, it declined by approximately 3 percent in the placebo group (P=0. 0026; Wilcoxon test). The average baseline percent predicted forced vital capacity in both groups was approximately 55 percent.

The results for both efficacy endpoints were consistent across various prospectively defined subgroups. ^[5]

References

External links

• United Pompe Foundation
• The website of the Pompe's Group of the Association for Glycogen Storage Disease (UK)
• International Pompe Association - A federation of Pompe disease patient's groups world-wide.
• Genzyme's Pompe Information site
• FDA Approval News for Myozyme
• Canadian Association of Pompe