Type VII Glycogen Storage Disease or Tarui's Disease

What Is Type VII Glycogen Storage Disease or Tarui’s Disease?

Tarui disease is known by many other names, such as glycogenesis 7, phosphofructokinase deficiency, GSD7, GSD VII, and glycogen storage disease type VII. Tarui’s disease is an inherited rare muscular metabolic disorder that is characterized by the inability to break down glycogen (a complex sugar) in the muscle cells. The name Tarui’s disease is named after the Japanese physician Seiichio Tarui (b.1927), who discovered this condition in 1965. The fluctuation in the muscle cells leads to difficulty in processing the carbohydrates needed for producing energy.

What Are the Types of Tarui’s Disease?

It is divided into four types:

• Classic Form: It is the most common type of Tarui’s disease. In this form, the kidneys are not able to process the uric acid, followed by damage that results from processing myoglobin.

• Late-onset Form: It is formed in the later stage of life, and the symptoms are visible in this form. Symptoms are visible from the age of 20 to 40 years and can vary in each individual.

• Infantile Form: As the name suggests, this form occurs in infants. It causes respiratory issues in some cases and increases the risk of death. Due to improper airways in infants, it can lead to suffocation.

• Hemolytic Form: In this form, the red blood cells break down prematurely (hemolytic anemia).

What Causes Tarui’s Disease?

Tarui’s disease occurs due to a genetic defect or mutation in the phosphofructokinase enzyme that affects the normal breakdown of glucose. The phosphofructokinase enzyme is divided into various subtypes and is found in various tissues of the body.

• PFKM Gene: The PFKM or phosphofructokinase muscle gene provides instructions to form one subunit of the phosphofructokinase enzyme, which is composed of these subunits of the PFKM gene. The main source of energy of the cells is stored as glycogen which can be broken down to simple sugar glucose for energy. The subunits of the PFKM are involved in this procedure.

At least 20 mutations in the PFKM gene lead to Tarui’s or glycogen storage type VII disease. The PFKM gene mutation leads to the production of PFKM subunits that have no function. If the PFKM subunits do not function properly or at all, then the phosphofructokinase is not formed generally in the muscles, and glycogen is also not able to break down normally. The partially broken-down glycogen builds up in the muscle cells, which leads to weakness.

What Are the Clinical Features of Tarui’s Disease?

The common symptoms seen in this condition include:

• Fatigue.

• Exercise intolerance.

• Hypotonia (decreased muscle tone).

• Cataract (a condition in which the eye's natural lens becomes cloudy).

• Joint contractures.

• Myopathy (muscle weakness due to muscle fiber dysfunction).

• Myoglobiniuria (acute muscle breakdown that causes dark-colored urine).

• Pain and cramping in the muscles.

• Moderate exercise leads to nausea and vomiting.

• Kidney failure in severe cases.

• Jaundice (yellowing of the skin).

What Is the Progression of Phosphofructokinase Deficiency?

Phosphofructokinase deficiency does not follow a typical progression. It can start in the teens to 30s. Unlike some diseases, it does not get worse over time. However, some people may feel weak between episodes of having trouble with exercise. This weakness usually happens later on in the disease.

What Are the Different Modalities Through Which Tarui’s Disease Is Diagnosed?

Some of the methods through which this condition can be diagnosed include:

• Genetic Testing - It examines the DNA, which is a database that carries instructions for the body’s functions. It is always informed before genetic testing that, in some cases, the negative result does not confirm the diagnosis, and the test can be performed again. Genetic testing helps in confirming the presence of a defective PKFM gene in an individual.

• Blood Test - A blood test is done to check the level of phosphofructokinase. A healthcare professional will take the blood from the arm’s vein. The whole procedure takes four to five minutes. Next, the blood sample is sent to the laboratory for further testing. After the results come, the expert will evaluate the level of phosphofructokinase.

• Muscle Biopsy - Muscle biopsy in Torai’s disease is done to diagnose the excess accumulation of glycogen. It is done in two ways. First, an open biopsy is done by removing one or more muscle tissues with the help of a sharp scissor. The second method used for muscle biopsy is needle biopsy, in which a pea-sized muscle sample is collected with the help of a needle. The sample is then sent to the laboratory, where the technician cuts it into fine pieces and, by using different chemical activities in tissues, helps examine and diagnose the condition.

What Are Some Other Disorders Similar to Phosphofructokinase Deficiency?

McArdle Disease - This is an inherited glycogen storage disorder due to missing muscle enzyme myophosphorylase. Symptoms include exercise intolerance, muscle cramping, and dark urine (myoglobinuria).

Pompe Disease - This is an inherited metabolic disorder due to a deficiency of enzyme acid alpha-glucosidase. Symptoms include muscle weakness and breathing difficulty from excess glycogen buildup in cells. It is also known as glycogen storage disease type 2.

Forbes Disease - Inherited glycogen storage disorder inherited in an autosomal recessive manner. Abnormal glycogen accumulates in the liver, muscles, and sometimes the heart.

How Is Tarui’s Disease Managed?

Some of the treatment options include:

• Genetic counseling can be given to the patient’s family to make them understand the severity of the condition and also help to make the family planning decision. It will be conducted by an expert who will guide and explain the condition's long-term and short-term features and the risk of recurrence in family members.

• A ketogenic diet such as seafood, eggs, and avocados improves symptoms of PFK deficiency in infants.

• Occupational therapy helps in regaining physical strength. An expert will help the patient by lifting light objects and walking.

What Is the Status of Research on Phosphofructokinase Deficiency?

Research on phosphofructokinase deficiency keeps going. With better tests, doctors can now spot the disease earlier and know more about how it affects people. Scientists are

• Trying to understand how the disorder works in the body and find ways to treat it.

• Looking at genes and molecules to figure out what goes wrong.

• Testing new treatments like gene therapy and enzyme replacement therapy.

Conclusion:

Tarui’s disease is a genetic disorder that affects muscle tone and causes weakness. There are different types of Tarui’s disease such as classic, late-onset, infantile, and hemolytic forms. It is caused by to genetic mutation in the PFKM gene that reduces the normal breakdown of glycogen for sugar. The symptoms in adults are visible from around 25 to 30 years of age and can be diagnosed with the help of muscle biopsy and genetic testing. Taking a ketogenic diet and occupational therapy helps in reducing the effects of the symptoms.