On this page
GSD VII (Tarui disease)
GSD VII affects how muscles use energy, leading to exercise intolerance, muscle pain, and sometimes weakness. It is a rare inherited condition, typically presenting in childhood or adolescence, that impacts individuals' physical activity levels.
Overview
Glycogen Storage Disease Type VII (GSD VII), also known as Tarui disease, is a rare inherited metabolic disorder. It primarily affects the skeletal muscles, which are the muscles responsible for movement. In individuals with GSD VII, the body cannot properly break down glycogen, a stored form of sugar, to produce energy in muscle cells [PMID:31828551]. This inability to use glycogen effectively means muscles run out of fuel during physical activity, leading to characteristic symptoms.
Symptoms & clinical features
Symptoms of GSD VII often become noticeable during childhood or adolescence, though onset can vary. A key feature is exercise intolerance, meaning individuals experience fatigue, muscle pain, and cramping after even moderate physical exertion [PMID:31828551]. Some people may also develop myoglobinuria, where muscle breakdown products are released into the urine, causing it to appear reddish-brown. This can sometimes lead to kidney problems. In severe cases, muscle weakness can be present even at rest, and some individuals may experience a 'second wind' phenomenon, where symptoms temporarily improve after a short rest period, allowing for continued activity for a limited time. In rare instances, a more severe form can present in infancy, with profound muscle weakness and potentially life-threatening complications.
Video: Genetics 101
Affected organs
GSD VII predominantly affects the skeletal muscles throughout the body. These are the voluntary muscles that enable movement, such as those in the arms, legs, and torso. The heart muscle (cardiac muscle) is generally not affected by this condition. The red blood cells may also be involved in some cases, which can lead to a type of anaemia called compensated haemolytic anaemia, where the body compensates for reduced red blood cell lifespan [PMID:25700863]. While the kidneys are not directly affected by GSD VII, severe episodes of myoglobinuria can put a strain on kidney function, potentially leading to kidney damage if not managed appropriately.
Risks & severity
The severity of GSD VII can vary significantly between individuals. Most commonly, symptoms are mild to moderate and involve exercise intolerance and muscle pain. However, some individuals can experience more severe episodes of rhabdomyolysis (severe muscle breakdown) leading to myoglobinuria, which carries a risk of acute kidney injury. The condition does not typically shorten lifespan, especially with appropriate management. The exact prevalence of GSD VII is not well established, but it is considered a very rare condition within the UK and globally.
Genetic causes
GSD VII is caused by genetic changes (pathogenic variants) in the PFKM gene. This gene provides instructions for making the muscle-specific phosphofructokinase (PFK) enzyme. PFK is a crucial enzyme involved in glycolysis, the process by which glucose (sugar) is broken down to produce energy. Specifically, the muscle PFK enzyme helps to convert fructose-6-phosphate into fructose-1,6-bisphosphate, a key step in extracting energy from glycogen in muscle cells [PMID:25700863]. When there are pathogenic variants in PFKM, the muscle PFK enzyme either does not work properly or is completely absent, disrupting the muscle's ability to use glycogen for energy. This leads to the accumulation of glycogen in muscle cells and insufficient energy production during activity.
Inheritance pattern
GSD VII is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the altered PFKM gene - one from each parent - to develop the condition. People who inherit only one copy of the altered gene are known as carriers. Carriers typically do not show symptoms of GSD VII because their single working copy of the gene is sufficient to produce enough functional enzyme [PMID:31828551]. If two carriers have a child together, there is a 25% chance with each pregnancy that their child will inherit two altered copies of the gene and develop GSD VII, a 50% chance that the child will be a carrier, and a 25% chance that the child will inherit two working copies of the gene and not be affected or a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of GSD VII typically begins with a clinical evaluation based on the characteristic symptoms of exercise intolerance, muscle pain, and potentially myoglobinuria. Blood tests may show elevated levels of creatine kinase (CK), an enzyme that indicates muscle damage. A muscle biopsy, where a small sample of muscle tissue is taken, can help confirm the diagnosis by revealing a deficiency of the phosphofructokinase enzyme and accumulation of glycogen. Definitive diagnosis is made through genetic testing, which identifies pathogenic variants in the PFKM gene. In the UK, such genetic testing would typically be requested by a clinical geneticist or a metabolic specialist. The NHS Genomic Medicine Service provides pathways for rare disease diagnosis, often utilising R-codes like R14 (inherited metabolic disorders) for genetic testing where appropriate.
Management & lifestyle
There is currently no cure for GSD VII, so management focuses on alleviating symptoms and preventing complications. Individuals with GSD VII are often advised to avoid strenuous exercise that triggers muscle symptoms and to identify their personal tolerance levels for physical activity. Some dietary modifications, such as a high-protein, low-carbohydrate diet, have been explored, with varying success. However, dietary advice should always be personalised and guided by a metabolic dietitian. Staying well-hydrated is important, especially during periods of activity, to help protect kidney function. Regular monitoring of kidney function may be recommended. Management often involves a multidisciplinary team, including neurologists, metabolic specialists, and physiotherapists. Genetic counsellors can provide essential support and information regarding the inheritance pattern and family planning options.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like GSD VII would typically be referred to a clinical genetics service or a specialist metabolic centre within the NHS. These services coordinate diagnostic investigations, including genetic testing through the NHS Genomic Medicine Service, often using specific R-codes for rare inherited metabolic disorders. Genetic counsellors play a vital role in explaining the genetic diagnosis, inheritance patterns, and implications for the wider family, as well as providing emotional support and signposting to patient support groups. Management plans are developed within a multidisciplinary team framework, ensuring comprehensive and integrated care.
Frequently asked questions
What is the 'second wind' phenomenon in GSD VII?
The 'second wind' phenomenon refers to a temporary improvement in symptoms after a short rest during exercise. Individuals might experience muscle pain and fatigue initially, but after a brief break, they can sometimes continue activity for a limited time before symptoms return. This is thought to be due to the body starting to use alternative fuel sources, such as fats, for energy.
Can diet help manage GSD VII?
Some dietary approaches, such as a high-protein, low-carbohydrate diet, have been explored for GSD VII. The aim is often to promote fat metabolism for energy. However, individual responses vary, and any dietary changes should always be discussed with a doctor or a metabolic dietitian to ensure they are safe and appropriate for your specific needs.
Is GSD VII always diagnosed in childhood?
While symptoms of GSD VII often begin in childhood or adolescence, the age of diagnosis can vary. Some individuals might experience milder symptoms that are not immediately recognised, leading to a later diagnosis. In rare cases, a more severe form can present in infancy.
What are the risks of myoglobinuria?
Myoglobinuria means that myoglobin, a protein from damaged muscle cells, is released into the urine. This can cause the urine to appear dark, often reddish-brown. Severe or repeated episodes of myoglobinuria can strain the kidneys and, in some cases, lead to acute kidney injury, which requires urgent medical attention.
Will my children inherit GSD VII if I have it?
GSD VII is inherited in an autosomal recessive pattern. If you have GSD VII, it means you have two altered copies of the PFKM gene. Your children will each inherit one altered copy from you. If your partner is not a carrier, your children will be carriers but will not have the condition. If your partner is also a carrier, there is a 50% chance for each child to be a carrier and a 25% chance to inherit GSD VII.