Pompe disease is a rare genetic disease characterized by the abnormal buildup of a sugar molecule called glycogen inside cells. This buildup impairs the working of different organs and tissues, especially the heart, respiratory, and skeletal muscles.

Causes

Glycogen is a form of sugar that the body stores in cells of the liver and skeletal muscles, and works as a long-term reserve of energy.

When the body needs energy, this large molecule is broken down into smaller molecules of a simpler sugar called glucose. Certain proteins — known as enzymes — are needed for this process. One of these enzymes is the acid alpha-glucosidase (GAA). A mutation in the GAA gene can either prevent the production of this enzyme, or create an enzyme that does not work as intended. In either case, glycogen cannot be broken down and builds to toxic levels inside cells, impairing certain organs and systems, particularly the muscles.

Inheritance

Pompe disease is inherited in an autosomal recessive pattern. This means the disease only develops in people who inherit two faulty copies of the gene, one from each parent.

People with only one faulty gene do not show disease signs or symptoms. They are called carriers because they can pass the disease onto their children. When both parents are carriers, there is 25 percent chance that a child will inherit both mutated copies of the gene and develop Pompe disease. Likewise, this child has 50 percent chance of inheriting one mutated gene and also becoming a carrier, and a 25 percent chance of inheriting two healthy genes and neither developing the disease nor being a carrier.

Types

There are three types of Pompe disease, classified according to disease severity and age of onset: classic infantile form, non-classic infantile form, and late-onset form.

Symptoms of classic infantile Pompe disease are evident within months of birth, while symptoms of the non-classic infantile form usually start to develop by a child’s first year of life. Late-onset Pompe disease may begin anytime from late childhood to adolescence, or even in adulthood.

Symptoms

Around one-third of Pompe patients have the infantile-onset form of the disease, which is due to a complete or almost complete lack of GAA enzyme. Symptoms include a slower growth rate (often due to feeding problems); muscular weakness; poor muscle tone (hypotonia); poor or absent reflexes; difficulties breathing, moving, and swallowing; and an enlarged tongue, liver, and heart. Without treatment, these patients often die at very young ages — 1 or 2 years old —  due to heart or respiratory complications.

Non-classical infantile Pompe disease is less common, and damage to heart muscle progresses more slowly in these babies.

The late onset form of Pompe disease is found in about two-thirds of all patients. It is milder because it is due to only a partial lack of the GAA enzyme. Symptoms include slow but progressive muscular weakness, particularly of muscles in the legs, trunk, and respiratory system, motor difficulties, breathing problems, fatigue, abnormal curvature of the spine. Life expectancy can be affected, but disease prognosis is highly variable among individuals.

Diagnosis

Pompe disease is typically first diagnosed based on clinical findings, particularly those related to breathing problems and evidence of muscular weakness. Differential diagnosis is important since Pompe disease may be wrongly assumed to be a different chronic and muscle-wasting disease.

Diagnosis can be confirmed by assessing the activity of the GAA enzyme in cells obtained from the skin, muscles, or blood. In children with infantile-onset Pompe disease, the activity of the GAA enzyme is less than 1 percent. In individuals with the late-onset form of this disease, GAA activity is typically lower than 40 percent.

Testing for GAA gene mutations can help confirm the diagnosis, and is particularly helpful in identifying carriers. Prenatal diagnosis may be available for couples with a child affected by the disease.

Treatment

Pompe disease patients are followed by a multidisciplinary team of specialists, including cardiologists, neurologists, pulmonologists, respiratory therapists, metabolic specialists, dietitians, orthopedists, occupational/speech therapists, geneticists, and genetic counselors.

Enzyme replacing therapy may help reduce the buildup of glycogen inside cells, and slow the progression of the disease.

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