Genetics of Tarui Disease (Glycogen-Storage Disease Type VII or Phosphofructokinase Deficiency) Workup

Updated: May 21, 2018
  • Author: Renee J Chosed, PhD; Chief Editor: Maria Descartes, MD  more...
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Laboratory Studies

Serum creatine kinase (CK) values are usually increased in patients with Tarui disease (glycogen-storage disease type VII).

Lactic acid levels do not increase following exercise.

Bilirubin levels may be elevated.

Reticulocyte count and reticulocyte distribution width (RDW) may be increased.

Urinalysis may reveal myoglobinuria, especially after exercise.


Imaging Studies

Brain imaging scans in patients with infantile-onset Tarui disease may show cortical atrophy and ventricular dilatation.

Phosphorus-31 nuclear magnetic resonance spectroscopy (31 P-NMR S) of calf muscle using a 4.7-Tesla MRI may be useful in diagnosis. During exercise, glycolytic intermediates accumulate as phosphorylated monoesters that are pathognomonic of Tarui disease. This study also shows the absence of lactic acid production. [21]


Other Tests


Electromyography (EMG) may reveal small-motor potentials of short duration consistent with myopathic changes.


Echocardiography may reveal valvular thickening, and ECG may reveal an arrhythmia.

Ischemic forearm test 

The ischemic forearm test is an important tool for the diagnosis of metabolic myopathies. The test is used to examine the metabolic pathways that provide energy for muscle function during anaerobic exercise.

First, a blood pressure cuff is placed on the patient's arm and is inflated above systolic pressure.

The patient is then instructed to repetitively grasp an object (once or twice per second) for 2-3 minutes.

Blood samples for creatine kinase, ammonia, and lactate and urine samples for myoglobin analysis are immediately obtained before and 5 minutes, 10 minutes, and 20 minutes after inflating the cuff.

Healthy patients have an increase in lactate levels of at least 5-10 mg/dL and an increase in ammonia levels of at least 100 mcg/dL, with return to baseline. If neither level increases, the exercise was not strenuous enough, and the test results are not valid.

An increased lactate level at rest (before exercise) is evidence of mitochondrial myopathy.

Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency. The failure of lactate to increase with ammonia is evidence of a glycogen-storage disease that results in blockage of a carbohydrate metabolic pathway.

Ischemic forearm test results may be positive in patients with Tarui disease, Cori disease (glycogen-storage disease type III), and McArdle disease (glycogen-storage disease type V).

Exercise test

The absence of a spontaneous second wind in a patient with suspected Tarui disease can be studied with an exercise test after an overnight fast. Continuous cycling for 15-20 minutes on a bicycle ergometer is maintained at a constant workload. Peak exercise capacity is determined after 6-8 minutes of exercise and again at 25-30 minutes of exercise. Heart rate is monitored continuously, and perceived exertion (Borg scale) is recorded during each minute of exercise. A spontaneous second wind is accompanied by decreased heart rate, perceived exertion, and increased oxygen consumption. Only patients with McArdle disease (glycogen-storage disease type V) exhibit a spontaneous second wind. A spontaneous second wind does not occur in patients with Tarui disease (glycogen-storage disease type VII), phosphoglycerate kinase deficiency, phosphoglycerate mutase deficiency, and certain mitochondrial disorders. [22]

Glucose or sucrose intake before exercise will exacerbate the muscle symptoms in patients with Tarui disease. Thirty minutes before an exercise test, a beverage containing 75 grams of sucrose is ingested or a glucose infusion of 6 ml per minute is begun. Carbohydrate intake increases the symptoms of exercise intolerance in Tarui disease. In contrast, carbohydrate decreases the symptoms of exercise intolerance in McArdle disease (glycogen-storage disease type V) and has no effect on phosphoglycerate mutase deficiency [22] .

Muscle biopsy

Muscle biopsy may reveal elevated glycogen content. Demonstration of decreased phosphofructokinase (PFK) enzyme activity in muscle tissue is considered definitive biochemical diagnosis of Tarui disease.

Genetic analysis

The demonstration of homozygous or compound heterozygous mutations in the PFKM gene by sequence analysis is considered definitive molecular diagnosis of Tarui disease. Targeted mutation analysis may be considered in Ashkenazi Jewish patients and when a familial mutation has been identified.



Muscle biopsy is necessary for microscopic and biochemical assay of PFK activity.


Histologic Findings

Glycogen accumulates between myofibrils under the sarcolemma, as in McArdle disease. Muscle glycogen content is typically greater than 1.5 g per 100 g wet muscle weight.

An abnormal polysaccharide, unique to Tarui disease, may also be found, especially in older patients. This polysaccharide is periodic acid-Schiff (PAS) positive but is not digested by diastase.

Nonspecific myopathic changes may also be observed.

In infantile-onset Tarui disease, little histological evidence of glycogen accumulation may be evident, but glycogen levels are typically more than twice the reference range.