What are the other Names for this Condition? (Also known as/Synonyms)

• Pulmonary Hypertension and Glycogen Storage Disease
• Pulmonary Hypertension in Glycogen Storage Disease
• Pulmonary Hypertension with Glycogen Storage Disease

What is Pulmonary Hypertension due to Glycogen Storage Disease? (Definition/Background Information)

• Pulmonary Hypertension (PH) is a disorder characterized by very high blood pressure (above normal) in the lungs due to a variety of causes. It should not be confused with systemic hypertension, otherwise known as ‘high blood pressure’
• The pulmonary blood vessels (arteries and veins) are usually a “low pressure” system, which means the blood pressure within the lung blood vessels is much lower than the rest of the body
• This elevated pulmonary blood pressure causes the right side of the heart to work harder, placing an increased burden on the heart. It is often caused by various lung and heart disease but can be associated with many other conditions too
• The World Health Organization (WHO) has clinically classified pulmonary hypertension according to certain groups. Pulmonary Hypertension due to Glycogen Storage Disease forms part of WHO group 5 (sub group 5.3. Metabolic disorders)
• The condition develops in association with a group of metabolic conditions termed glycogen storage diseases (GSDs), which arise due to abnormalities in glycogen storage; glycogen is a form of glucose. GSDs are inherited genetic disorders that typically manifest during early childhood. There are over 10 different types of glycogen storage disorders
• The signs and symptoms of Pulmonary Hypertension due to Glycogen Storage Disease may include shortness of breath, chest pain, fatigue, and dizziness. The signs and symptoms also depend on the specific form of underlying glycogen storage disease, but may generally include low blood sugar, enlarged liver, muscle weaknesses, and growth failure
• Following a diagnosis of Pulmonary Hypertension due to Glycogen Storage Disease, the treatment measures may involve the use of medications, such as calcium channel blockers, and bringing about certain lifestyle modifications, among others. Glycogen storage disease is treated using proper food control (modified diets) and medications
• The prognosis of Pulmonary Hypertension due to Glycogen Storage Disease may be improved if the condition is diagnosed promptly and treated appropriately. However, the overall prognosis depends on several factors including on the type and severity of the underlying glycogen storage disease; it may vastly vary from one individual to another

Who gets Pulmonary Hypertension due to Glycogen Storage Disease? (Age and Sex Distribution)

• The age, gender, and racial/ethnic distribution of Pulmonary Hypertension due to Glycogen Storage Disease depends on the underlying glycogen storage disease type
• The incidence of GSD varies in the general population but is reportedly observed in between 1 in 20,000 to 40,000 births
• Both males and females are at equal risk for the condition
• All racial and ethnic groups may be affected, but some communities show a higher incidence rate (such as Mexicans)

The association of GSD with pulmonary hypertension is extremely rare, and only a few cases have been reported worldwide.

What are the Risk Factors for Pulmonary Hypertension due to Glycogen Storage Disease? (Predisposing Factors)

The risk factors for Pulmonary Hypertension due to Glycogen Storage Disease are dependent on the respective risk factors of glycogen storage disease:

• A positive family history of Gaucher disease is a major risk factor
• Some populations, such as the Mexicans, may have a higher risk for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pulmonary Hypertension due to Glycogen Storage Disease? (Etiology)

Pulmonary hypertension is caused by an increased blood pressure within the blood vessels of the lung. Pulmonary Hypertension due to Glycogen Storage Disease is associated with the underlying glycogen storage disease; it develops secondary to the condition.

The cause of glycogen storage diseases is due to certain inherited genetic defects. GSDs are hereditary genetic disorders that typically run in families.

• In individuals with glycogen storage disease, the serotonin hypothesis exists
• It is reported that vasoconstrictive properties of serotonin act on pulmonary vasculature and contribute to PH

What are the Signs and Symptoms of Pulmonary Hypertension due to Glycogen Storage Disease?

The signs and symptoms of Pulmonary Hypertension due to Glycogen Storage Disease depends on a set of several factors that include age of the individual, overall health of the individual, and associated health conditions. The signs and symptoms can be directly related to pulmonary hypertension, and to the underlying glycogen storage disease.

The common signs and symptoms of pulmonary hypertension include:

• Progressive shortness of breath (especially while exercising), is the most common symptom
• Fatigue (frequent tiredness)
• Chest pain
• Dizziness and fainting
• Swelling of the ankles/legs
• Palpitations
• Bluish lips and skin, observed during the later stages
• Irregular heartbeat (arrhythmias)
• Fluid in the abdomen (ascites)

There are several types of glycogen storage diseases. The signs and symptoms depend on its severity and type, but may commonly include:

• Muscle weaknesses and cramping
• Enlarged liver or hepatomegaly
• Reduced blood sugar or hypoglycemia
• Failure to grow (in children)

Often, the detection of the associated condition may help in determining the cause of pulmonary hypertension. In many cases, the signs and symptoms due to glycogen storage disease and the subsequent development of pulmonary hypertension may be overlapping.

How is Pulmonary Hypertension due to Glycogen Storage Disease Diagnosed?

To diagnose Pulmonary Hypertension due to Glycogen Storage Disease, a diagnosis of pulmonary hypertension (PH) must first be established. This involves certain preliminary diagnostic procedures. Depending on the results of these tests, confirmation will be made with a right-heart catheterization. After a diagnosis of PH is made, the healthcare provider may undertake further tests to diagnose glycogen storage disease, if necessary.

The preliminary procedures may include:

• A complete physical examination of the patient 
• A thorough checking of the patient’s medical history and a detailed checking of the family history of the patient
• Blood tests:
  • Blood tests help rule out other diseases
  • They also help in checking the blood oxygen levels
  • The measurement of brain natriuretic peptide (BNP) can be used to assess the strain on one’s heart
• Chest X-ray: Chest X-rays can reveal structural signs of pulmonary hypertension by identifying changes in the pulmonary arteries or enlargement of the right side of the heart
• Electrocardiogram (ECG): An electrocardiogram checks the electrical impulses of the heart. There are certain identifiable patterns on an ECG that may indicate pulmonary hypertension. However, ECG is not specific enough to diagnose the condition by itself, so a combination of tests may be recommended by the healthcare provider
• Echocardiogram: In this procedure, a sonogram of the heart is taken and used to measure overall functioning as well as measure the pressure within the chambers of the right heart. An echocardiogram is also often times used to monitor a patient’s condition after diagnosis and during treatment
• Pulmonary function tests: These tests help measure the quality of breathing and check the functioning of the lungs (such as how much air is breathed in and out, as well as the quality of oxygen exchange)
• Exercise tolerance test (six-minute walk test): This helps to measure the patient’s ability to exercise
• Nuclear scan (ventilation/perfusion scan or V/Q scan): This tool helps identify any new or chronic blood clots in the vessels of the lungs that could be causing pulmonary hypertension

A diagnosis of glycogen storage disease may additionally involve:

• Blood tests (specific to the condition type)
• Urine tests
• Radiological studies of the affected regions
• Tissue biopsy, as needed
• Molecular genetic testing

The gold standard for pulmonary hypertension diagnosis and management is right-heart catheterization and acute vasodilator challenge.

• Right-heart catheterization:
  • If pulmonary hypertension is suspected based off preliminary tests and procedures, a right-heart catheterization test is ordered to help confirm the diagnosis
  • This test can accurately quantify right-heart pressures (measure the pressure within the chambers of the right heart), especially the pressure inside the pulmonary arteries
  • During this procedure, a very small catheter is inserted into a large vein (either within the patient’s groin or neck) and passed into the patient’s heart and vasculature to measure the internal blood pressures 
• Vasodilator study (acute vasodilator challenge):
  • While this test is not used to necessarily “diagnose” pulmonary hypertension, it is used to evaluate the patient for possible therapeutic management
  • Like right-heart catheterization, a catheter is placed within the pulmonary artery to test for vasodilation (or relaxation) in response to a class of medications called calcium channel blockers (CCBs)
  • The response and dosing of CCBs can be evaluated with this procedure

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pulmonary Hypertension due to Glycogen Storage Disease?

The complications of Pulmonary Hypertension due to Glycogen Storage Disease depends on a set of several factors that include the age of the individual, overall health of the individual, underlying glycogen storage disease, and promptness of diagnosis. 

Following are the possible complications that may arise due to the condition:

• Right-sided heart failure with hepatic congestion (due to deposition of stones in the liver)
• Pedal edema: Swelling of the leg or ankle
• Pleural effusions: Building-up of excess fluid around the lungs
• Worsening dyspnea (shortness of breath) upon exertion

The complications related to glycogen storage disease depend on the specific type of the disease, but may include:

• Severe hypoglycemia
• Retarded growth
• Easy bruising
• Low muscle tone
• Heat intolerance
• Liver abnormalities

How is Pulmonary Hypertension due to Glycogen Storage Disease Treated?

The treatment of Pulmonary Hypertension due to Glycogen Storage Disease depends on a set of several factors that include the severity of the signs and symptoms, age of the individual, and overall health of the individual.

• A treatment of the underlying metabolic condition (glycogen storage disease) is essential
• The management of GSD involves following a strict diet regimen and treating the symptoms

PH associated with Glycogen Storage Disease is best treated at a medical center with appropriate expertise. Several medical treatments are highlighted below:

• Conventional medical therapies:
  • Calcium channel blockers (CCBs): These are a group of medications that help vasodilate (or relax) the arteries. However, CCBs are only appropriate for patients demonstrating a favorable response to the vasodilator study
  • Inotropic agents: These are medications that assist in the pumping of the heart 
  • Diuretics, salt limitation, and weight monitoring may be recommended, to limit excess strain on the heart
  • Supplemental oxygen may help an individual meet the ‘oxygen needs’ for normal daily activities
  • Blood thinners: These medications help prevent blood clots, especially in the lung blood vessels
  • Treating underlying diseases or conditions
• Oral, inhaled, subcutaneous, or intravenous treatment options:
  • Endothelin receptor antagonists (ERAs) help in preventing pulmonary blood vessels from narrowing which helps keep the pressures towards normal levels
  • Phosphodiesterase inhibitors (PDE 5 Inhibitors), prostacyclin analogues, and soluble guanylate cyclase (sGC) stimulators, all aid in allowing vessels of the lungs to vasodilate (or relax)
• Additional treatment options may include:
  • Lifestyle modifications, such as nutrition, exercise, avoiding tobacco, and limiting alcohol consumption, are beneficial
  • Judicious exercising may be effective in limiting deconditioning (by building stamina), improving the quality of life, and exercising capacities. Isometric exercises, such as heavy weightlifting, should be avoided
  • Other treatments, depending on the etiology (cause) of pulmonary hypertension, may include various cardiothoracic procedures
  • Lung transplantation may be required with advanced forms of the disorder

How can Pulmonary Hypertension due to Glycogen Storage Disease be Prevented?

Pulmonary Hypertension due to Glycogen Storage Disease may be prevented or controlled if appropriate treatment of the underlying glycogen storage disease (GSD) is considered. However, presently, it is not possible to prevent the development of GSDs.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child

The non-modifiable risk factors for pulmonary hypertension (PH), such as age, gender, and genetics (family history), cannot be controlled; and therefore, it may not be possible to prevent PH that develops from these factors. However, an early and effective treatment is critical and imperative.

• For those with a pre-existing condition that is a risk factor for pulmonary hypertension, seeking medical attention at the onset of symptoms may help avoid worsening of the condition and complications 
• Avoidance of recreational drugs, various toxic agents, and inappropriate weight loss drugs is important

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis Pulmonary Hypertension due to Glycogen Storage Disease? (Outcomes/Resolutions)

• The prognosis of Pulmonary Hypertension due to Glycogen Storage Disease differs from one individual to another, depending on its severity and on the type and extent of underlying glycogen storage disease
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications. Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Pulmonary Hypertension due to Glycogen Storage Disease:

The following DoveMed website links are useful resources for additional information:

https://www.dovemed.com/diseases-conditions/glycogen-storage-disease-type-12/

https://www.dovemed.com/diseases-conditions/glycogen-storage-disease-type-1b/