Introduction
Pompe disease is an uncommon illness spectrum that manifests at various ages and with varying rates of disease development. From infancy to late adulthood, the onset of symptoms can happen at any age. Greater disease severity and quicker disease progression are often linked to earlier rather than later onset. Skeletal muscular weakness, which impairs movement and affects the respiratory system, is a defining feature of the illness across all age groups.
Infants most badly afflicted typically show symptoms within the first three months of their lives. They have less than two years to live if left untreated (classic infantile Pompe disease), along with typical heart abnormalities (dysfunction owing to heart enlargement) and generalized skeletal muscle weakening. Less severe types of Pompe disease that begin in childhood, adolescence, or adulthood seldom cause cardiac difficulties but eventually impair breathing and make walking difficult.
What Is Pompe Disease?
Glycogen, a complex sugar molecule, accumulates within cells in Pompe disease, a rare genetic condition that impairs cell function and causes issues with several organs, most notably the heart. Heart-related symptoms are present in all Pompe disease patients; however, heart failure risk is higher in the typical infantile-onset form. Although they have cardiomegaly or an enlarged heart, children with non-classic infantile-onset Pompe syndrome are less likely to develop heart failure. Patients with the late-onset version of the illness have a lower risk of heart failure, but they also have a higher chance of cardiomegaly and irregular heartbeats.
What Are Lysosomes and What Do They Do?
Molecules like lipids and carbohydrates are broken down and recycled by certain proteins (enzymes) in lysosomes. Lysosomal storage disorders are caused by deficiencies in one or more of these enzymes, preventing them from breaking down molecules in a way essential for normal cell function.
What Causes Pompe Disease?
The underlying cause of Pompe's illness is a mutation in the GAA gene, which results in a lack of the protein acid maltase. Complex sugars are not adequately broken down by acid maltase within the body's cells due to mutations in the GAA gene. These sugars and other chemicals build up in the body's tissues and organs, especially the muscles, which results in Pompe's illness. Because of the autosomal recessive mode of inheritance for this genetic disorder, each afflicted kid inherits one faulty copy of the GAA gene from each parent.
What Are the Symptoms of Pompe Disease?
Pompe disease comes in two flavors:
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Late-onset Pompe disease.
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Infantile Pompe disease.
Infantile Pompe Disease:
Infancy is when infantile Pompe disease symptoms first manifest. There are two other classifications for infantile Pompe disease: classic and non-classic. Symptoms of infantile Pompe illness start to show very soon after birth. The signs of non-classic infantile Pompe illness usually occur within the first year of life but might appear later.
Possible symptoms include:
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Muscular wasting (myopathy).
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Hypotonia, or low muscular tone.
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Hepatomegaly, or enlarged liver.
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Cardiac abnormalities.
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Inadequate development and weight gain (inability to flourish).
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Breathing problems.
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Heart failure within the first year of life can result from typical infantile Pompe disease if treatment is not received.
Late-onset Pompe Disease:
Possible symptoms include:
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Progressive myopathy, or muscle weakening.
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Severe exhaustion and cramping in the muscles.
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An irregular gait.
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Difficulty with movement.
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Respiratory issues.
What Are the Cardiac Effects of Pompe Disease?
The following are the cardiac effects of Pompe disease:
1. Cardiomegaly:
With this form of Pompe illness, the heart muscle can expand, although cardiac failure is not frequently the result. Conversely, muscle weakness can lead to serious respiratory problems, and non-classic infantile-onset Pompe illness can be deadly if left untreated. Patients with the late-onset version of the illness have a lower risk of heart failure, but they also have a higher chance of cardiomegaly and irregular heartbeats.
2. Left Ventricular Hypertrophy:
The buildup of glycogen in the heart muscle results in left ventricular hypertrophy and hypertrophic cardiomyopathy, thickening the ventricles and interventricular septum walls. Specifically, the left ventricle posterior wall's thickness grows considerably over time.
What Are the Treatment Modalities That Are Used in the Treatment of Pompe Disease?
Enzyme Replacement Therapy:
Enzyme replacement therapy (ERT), which includes introducing synthetic GAA enzymes into the circulation, is the primary treatment for Pompe disease. This medication for Pompe illness can assist in increasing muscular performance, decreasing the buildup of glycogen in the cells, and increasing survival time. The average life expectancy after therapy for Pompe's illness is five times greater.
Avalglucosidase alfa-night for babies and Lumizyme for adults comprise the ERTs available for infantile-onset and late-onset Pompe illness.
Supportive Therapy:
Apart from replacing enzymes, Pompe disease therapy is frequently intricate and contingent upon the severity of the symptoms. Patients often need a multidisciplinary team of experts, such as pediatricians, physical therapists, neurologists, and cardiologists.
For Pompe's illness, supportive therapies might consist of:
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To assist with breathing issues and respiratory treatment.
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Maintaining muscular strength and mobility via physical therapy.
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Occupational therapy can help with everyday tasks.
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Speech therapy to enhance verbal abilities.
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Nourishment to guarantee proper development and growth.
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Cardiac drugs to treat cardiac issues.
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Painkillers for the treatment of muscular soreness.
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Drugs for the bones to stop osteoporosis.
Preventive Therapy:
Those who carry the GAA gene mutation or have a family history of Pompe disease may benefit from genetic counseling to better understand their child's chance of developing the condition. Through the examination of cells obtained from amniocentesis or chorionic villus samples, prenatal testing can also identify Pompe's illness in an unborn child. GAA enzyme activity in blood samples is used in newborn screening for Pompe disease, which detects the condition in neonates soon after delivery.
Conclusion
In patients with the typical infantile form of Pompe disease, a lysosomal storage disorder brought on by a lack of the enzyme acid alpha-glucosidase, heart failure was the primary cause of mortality prior to the development of enzyme replacement therapy (ERT). Glycogen builds up gradually throughout the body, mostly in the heart, skeletal muscles, and other tissues. This is a characteristic feature of the condition. The most severe classic-infantile form of Pompe disease results in total alpha-glucosidase deficiency. The illness manifests clinically as a range of symptoms.
