POMPE DISEASE edit
The 'Pompe disease' is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally.it is an autosomal-recessive disorder that results from deficiency of acid alpha-glucosidase (also known as acid maltase), a lysosomal hydrolase.The Pompe Disease may also be called as 'Acid alpha glucosidase (GAA) deficiency' or 'Acid maltase deficiency (AMD)' or 'Glycogen storage disease type II'.
History edit
The Danish pathologist Joannes Cassianus Pompe first described this disease in 1932 when he was presented with a 7-month-old girl who died after developing idiopathic hypertrophic cardiomyopathy. Pompe observed an abnormal accumulation of glycogen in all postmortem tissues examined and described the cardinal pathologic features of this lysosomal storage disorder.
Classification edit
There are three types of Pompe Disease namely :
- Classic infantile-onset
- Non-classic infantile-onset
- Late-onset.
The 'Classic form of infantile-onset' begins within a few months of birth. Infants with this disorder typically experience muscle weakness (myopathy), poor muscle tone (hypotonia), an enlarged liver (hepatomegaly), and heart defects. Affected infants may also fail to gain weight and grow at the expected rate (failure to thrive) and have breathing problems.
The 'Non-classic form of infantile-onset' usually appears by age 1. It is characterized by delayed motor skills (such as rolling over and sitting) and progressive muscle weakness. The heart may be abnormally large (cardiomegaly), but affected individuals usually do not experience heart failure.
The 'Late-onset type' may not become apparent until later in childhood, adolescence, or adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this disorder and is less likely to involve the heart. Most individuals with late-onset Pompe disease experience progressive muscle weakness, especially in the legs and the trunk, including the muscles that control breathing.
Causes edit
The underlying cause of Pompe disease is always the same in all patients: the absence or marked deficiency of a specific enzyme, acid alpha-glucosidase (often abbreviated GAA).This accumulated glycogen affects muscle structure and function and results in muscle weakness. Exactly which areas of the body are affected, and how severely, may vary from patient to patient. The human body produces various enzymes that help break down substances that play a role in the function of cells throughout the body. This breakdown process occurs in small compartments within the cells called lysosomes. One particular enzyme, acid alpha-glucosidase, is responsible for breaking down glycogen in the lysosome. In patients with Pompe disease, this enzyme is either missing, deficient or not functioning properly.The GAA gene is responsible for the production of the enzyme acid alpha-glucosidase. When there is a mutation, or defect, in this gene, the enzyme is not be produced in sufficient amounts or does not function properly. Pompe disease occurs when a person inherits this gene defect from both parents.
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How are muscles affected? edit
As excess glycogen builds up, the cell’s lysosomes begin to swell beyond their normal size and can interfere with normal muscle function. In addition, lysosomes can rupture causing cellular damage. Damage to individual muscle cells eventually results in weakness of larger muscle bundles, leading to patients’ symptoms. The symptoms typically get worse over time, as more glycogen accumulates and the destructive process continues.
Inheritance Pattern edit
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Symptoms edit
Infantile Form
Individuals with the infantile form are the most severely affected. Although these infants usually appear normal at birth, the disease presents within the first two or three months of life with rapidly progressive muscle weakness, diminished muscle tone (hypotonia), and a type of heart disease known as hypertrophic cardiomyopathy, a condition characterized by abnormal thickening of the walls of the heart resulting in obstruction of blood flow in and out of the heart. In most cases, the left ventricle is affected. Symptoms of hypertrophic cardiomyopathy vary widely among affected individuals. Affected infants and children may experience shortness of breath upon exertion, fatigue, excessive sweating, and poor appetite and weight gain resulting in growth failure. As affected children age, they may experience chest pain or discomfort, irregular heartbeats, dizziness or fainting episodes (syncope) usually upon heavy exertion, and, eventually, congestive heart failure and fluid accumulation within the lungs. In some cases, affected individuals may experience sudden cardiac arrest and, potentially, sudden death.
Many infants have a large, protruding tongue and a moderate enlargement of the liver. Infants may appear floppy and may be unable to move their arms and legs properly.
Late Onset Forms
Late onset Pompe disease is generally associated with progressive proximal muscle weakness, varying degrees of respiratory weakness and little to no cardiac involvement. The lower limbs are affected more often than the upper limb. The disease progresses more slowly than the infantile form. However, progressive muscle weakness can eventually cause serious complications including swallowing difficulties, difficulty walking and severe respiratory failure. Respiratory tract infections may be frequent.Initial symptoms may include headache at night or upon awakening, sleeping difficulties including sleep apnea, nausea, fatigue, difficulty breathing except in an upright position (orthopnea), and labored breathing upon exertion (exertional dyspnea).
Diagnosis edit
The diagnosis of Pompe disease is based upon a thorough clinical evaluation, a detailed patient and family history, and a variety of tests. Prenatal diagnosis is possible when a pregnancy is believed to be at risk for Pompe disease.
In individuals suspected of having Pompe disease, a blood sample (dried blood spots) can be taken and an enzyme assay, a test that measures the activity of a specific enzyme, can be performed. An enzyme assay can also be performed on drawn blood, in which the enzyme activity of GAA is measured in certain white blood cells called lymphocytes. These exams are a reliable and convenient means of diagnosing Pompe disease.When a diagnosis of Pompe disease is based upon a blood-based enzyme assay, it must be confirmed through molecular genetic testing or by another assay on a separate blood or tissue sample. Molecular genetic testing can detect mutations in the GAA gene that causes Pompe disease.
Treatment edit
The treatment of Pompe disease is both disease-specific and symptomatic and supportive.
Respiratory support may be required, as most patients have some degree of respiratory compromise and/or respiratory failure. Physical therapy may help to strengthen respiratory muscles. Some patients may need respiratory assistance during the night or periods of the day or during respiratory tract infections may be helpful. Some patients may require mechanical ventilation support, which can include noninvasive and invasive techniques.
Physiotherapy is recommended to improve strength and physical ability. Occupational therapy, including the use of canes or walkers, may be necessary. Eventually, some individuals may require the use of a wheelchair. Speech therapy can be beneficial to improve articulation and speech in some cases.