Type II Glycogen Storage Disease - Causes, Symptoms, Diagnosis, and Treatment

Introduction

Glycogen storage disease is a rare metabolic and genetic disorder. It is characterized by failure of the body to store and disintegrate glycogen (a storage form of glucose). The failure to break down and store glycogen is due to an inherited deficiency of enzymes needed to metabolize glycogen. Many enzymes are required to metabolize glycogen. So there is a set of enzymes involved in the process. Hence their deficiencies can lead to several glycogen storage diseases.

What Is Type 2 Glycogen Storage Disease or Pompe Disease?

Pompe disease is a form of glycogen storage disease due to deficiency of enzyme alpha-glucosidase. Glycogen is broken down into simpler molecules by this enzyme. So a deficiency of the enzyme results in the accumulation of glycogen in the body tissues. The special storage cells called lysosomes contain the enzymes that help break down sugars and fats. The lysosomes sometimes lack the enzymes or have a defective form of enzyme that cannot function normally to metabolize glycogen. This disease is also called lysosomal storage disease (LSD).

What Is the Cause of Pompe Disease?

A genetic mutation of a gene coding for the enzyme alpha-glucosidase causes Pompe disease. The gene GAA is mutated. The enzyme is also called acid maltase. This enzyme degrades the complex glycogen molecules into simpler glucose molecules for the energy requirement of the body. There are 2 types of Pompe disease:

1. Infantile-onset Pompe disease.

2. Late-onset or delayed-onset Pompe disease.

The infantile-onset Pompe disease can be either classic type or non-classic type.

What Is Inheritance Pattern of Pompe Disease?

The disease has an autosomal recessive pattern of inheritance. That means each parent carries one copy of the defective gene and passes down their copy of a gene to their child. The parents are carriers of the gene so do not show any signs of the disease whereas the child who received both the defective copies of the mutated gene shows the signs and symptoms of the disease. So with each pregnancy, there is a 25 % chance of a child getting affected and a 25 % chance of a child being normal and healthy. And there is a 50 % chance of a child being a carrier of the disease.

What Are the Signs and Symptoms of Pompe Disease?

• The classic type of infantile-onset Pompe disease shows symptoms soon after birth that is in the first few months.

  1. Muscle weakness.

  2. Weak muscle tone.

  3. Enlargement of the liver.

  4. Lack of physical growth according to age.

  5. Failure to thrive and gain weight.

  6. Difficulty in breathing.

  7. Difficulty in feeding.

  8. Hearing problem.

  9. Recurrent infection in the respiratory pathway.

• The non-classic infantile type of Pompe disease shows symptoms from 1 year of age.

  1. Delayed development of motor skills like crawling and walking.

  2. Progressive weakness of muscles.

  3. A problem breathing.

  4. Cardiac enlargement.

• The late-onset Pompe disease typically shows signs and symptoms from late childhood or even during teenage years.

  1. Steady weakness of limbs and trunk.

  2. Breathing issues.

  3. Enlargement of the heart.

  4. Difficulty in walking.

  5. Pain over a large group of muscles.

  6. Inability to exercise.

  7. Increased tendency to fall.

  8. Recurrent respiratory infections.

  9. Shortness of breath on exertion.

  10. Feeling fatigued throughout the day.

  11. Waking up with a headache in the morning.

  12. Consistent weight reduction.

  13. Difficulty in swallowing.

  14. Loss of hearing.

  15. Irregularity in a heartbeat.

How Is Pompe Disease Diagnosed?

The presentating signs and symptoms of this disease is very similar to other disorders making its diagnosis difficult clinically. They resemble myopathies and diseases affecting neuromuscular junctions.

1. History of Pressenting Illness and Past Illnesses: A complete patient history, family history, and clinical evaluation are done to initiate the diagnosis process.

2. Blood Tests: An elevated level of creatine kinase (CK) is present in the blood.

3. Genetic Testing: A DNA analysis of the alpha acid glucosidase gene (GAA) can accurately diagnose the disease. A known family history will be useful in diagnosing the disease and initiating an enzyme analysis test to confirm.

4. Electromyography: This test determines the functioning of the muscles. It will indicate the muscular pathology of Pompe disease.

5. Pulmonary Function Tests: These are tests done to examine lung capacity.

6. Cardiac Investigations: These tests include X-rays, electrocardiograms, and echocardiograms to examine heart functions.

7. Prenatal Screening: Prenatal testing of the developing fetus is done to check the pregnant women at risk of developing the disease and with a known family history of Pompe disease.

What Is the Treatment for Pompe Disease?

A panel of specialists is required to work in an integrated manner to treat and manage patients with Pompe disease. Pulmonologists, neurologists, cardiologists, and other supportive medical professionals should be consulted regularly to manage the symptoms. Regular monitoring of heart and lung function should be performed. A promising treatment option is intravenous administration of alglucosidase alfa which is a genetically engineered enzyme. This is similar in structure and function to the naturally present enzyme alpha-glucosidase. This treatment is called enzyme replacement therapy (ERT). It is recommended to start ERT in infantile-onset Pompe disease before the patients display severe symptoms involving the heart and lungs. It is the only Food and drug administration (FDA) approved treatment for Pompe disease. The standard dose is 20 milligrams per kilogram of body weight given twice a week.

What Are the Complications of Pompe Disease?

This disease lacks definitive treatment, so the patients have to be diagnosed early and appropriately managed by a group of specialists. Without any treatment, there is a high chance of morbidity and mortality. The patients have compromised cardiac and lung health and weak muscles. They also have limited mobility due to poor muscle function. Muscle weakness can lead to respiratory arrest over a few years and cause death. Affected people will need to use wheelchairs and oxygen supplements.

Conclusion

The affected individuals live up to normal life expectancy when they are diagnosed with the disease early and given the right treatment. The treatment options available so far are only supportive. Research works are in progress in preclinical and clinical stages to discover newer and advanced treatments for this type of glycogen storage disease. At present only supportive treatment is available.