McArdle's disease

Classification according to ICD-10
E74.0	Glycogen storage disease (glycogenosis) McArdle's disease
ICD-10 online (WHO version 2019)

The disease McArdle (McArdle myopathy, McArdle's disease, McArdle's disease), also known as glycogen storage disease type V (GSD5) is glycogen storage disease , which in 1951 by the pediatrician Brian McArdle has been described (1911-2002) for the first time. This is due to a defect in the isoform of the enzyme glycogen phosphorylase , which is found in the skeletal muscles and is also known as myophosphorylase. The disease is autosomal - recessive inherited.

Pathogenesis

Muscle biopsy with enzyme histochemistry for myophosphorylase in A: normal muscle and B: McArdle's disease (lack of enzymatic activity)

There is an energy utilization disorder in patients with this disease. The polysaccharide glycogen is used to store and provide the energy carrier glucose in the muscles . The function of myophosphorylase is to mobilize glucose residues from the glycogen and thus make them available for energy production in the context of glycolysis or the oxidative citric acid cycle . If this depletion of glucose is disturbed by an enzyme defect , there is an accumulation of glycogen and, especially when the muscles are exerted, the muscles are insufficiently supplied with energy.

Symptoms

Symptoms already appear in young adulthood. Characteristic are a reduced resilience of the muscles ( myasthenia ), muscle pain ( myalgia ), muscle stiffness and cramps. The complaints arise either after short-term heavy use of the muscles (strength training, carrying heavy loads), or after less heavy, but long-lasting loads (running, hiking). Moderate muscle loads, on the other hand, can be sustained for a relatively long time without any noticeable discomfort. Many sufferers report that taking a break after the first onset of symptoms leads to good muscle resilience with few symptoms. This effect is characteristic and is called the second wind phenomenon in English .

Some patients also report darkening of the urine after exercise. This is an accumulation of muscle breakdown products in the urine ( myoglobinuria ) as a result of the increased muscle damage ( rhabdomyolysis ), since the tissue integrity of the muscles cannot be maintained due to the lack of energy. In severe cases, myoglobinuria can lead to acute kidney failure .

diagnosis

As a non-specific sign of muscle damage, the blood concentration of creatine kinase (CK) is increased, especially after physical exertion. There are also increases in ammonia and uric acid levels . Exposure under anaerobic conditions does not lead to an increase in lactate in the blood, but to a sharp increase in ammonia. This can indicate a disruption of the glycogen breakdown in the muscle cell, but is not a pathognomonic sign of McArdle's disease, because similar constellations of findings can also be found in other enzymatic disorders of the glycogen breakdown.

In the muscle biopsy , an increased glycogen storage in the muscle fibers can be detected histologically in the PAS staining . There is often selective atrophy of the type I muscle fibers. Sub-sarcolemmal vacuoles and peculiar disorders of the intermyofibrillary network in the NADH staining, the so-called linearizations, are typical. From an enzyme histochemical point of view , the activity of phosphorylase is significantly reduced or abolished. The diagnosis can, if necessary, be further substantiated by molecular genetic tests to detect a PGYM mutation.

McArdle's disease can also be diagnosed without the surgical intervention of a muscle biopsy with the help of non-invasive 31 phosphorus magnetic resonance spectroscopy (31P-MRS) in combination with a moderate muscle stress test. The 31P-MRS determines the energy-rich phosphates and the intracellular pH value in the muscle during exercise. A healthy muscle with an intact glycolytic metabolism forms so much lactate parallel to the breakdown of phosphocreatine (PKr) that, after a brief initial increase in pH, a decrease in the intracellular pH value can be recognized on the basis of the spectra. Glycolytic ATP formation delays the rate of degradation of PKr in healthy individuals in the course of constant exercise. The concentration of ATP remains constant in healthy people during exercise. The recovery speed of the PKr after exercise reflects the oxygen-dependent metabolism in the muscle, which in healthy people depends on the level of training. Lactate formation is absent in patients with muscle glycogenosis. The pH value therefore rises continuously in the course of muscle contraction as a result of the PKr degradation up to values ​​of 7.3. The rate of PKr degradation is not delayed, but very often even increases in the course of constant exposure. In most cases, the concentration of ATP in the muscle also decreases. Recovery of PKr after exercise is often pathologically delayed in patients with McArdle's disease. A deficiency in glycolysis enzymes differs from a deficiency in primary glycogen breakdown in the accumulation of sugar phosphates during exercise.

therapy

A causal therapy is not yet available. Physiotherapy can be useful if the muscles are permanently weak . In the foreground, however, is the attempt to influence diet through the targeted supply of glucose or fructose shortly before or during physical exertion. By endurance training below the anaerobic threshold a significant improvement in performance can be achieved. In a small clinical study, low-dose creatine treatment was associated with a significant improvement in muscle discomfort compared to placebo. Life expectancy is not significantly affected.

Web links

• Detailed description by Carsten Schröter

Individual evidence

1. ^ McArdle: Myopathy due to a defect in muscle glycogen breakdown. In: Clinical Science. 1951, 10: pp. 13-33.
2. ^ Pongratz et al.: On the morphology and biochemistry of glycogenosis type V (McArdle). In: J Mol Med 1981; 59 (18), pp. 1432-1440.
3. ↑ Vorgerd et al.: Mutation analysis in myophosphorylase deficiency (McArdle's disease). In: Ann Neurol. 1998; 43 (3), pp. 326-331. PMID 9506549
4. ↑ Zange et al .: Breakdown of adenine nucleotide pool in fatiguing skeletal muscle in McArdle's disease: A noninvasive 31P-MRS and EMG study. In: Muscle Nerve. 2003; 27, pp. 728-736.
5. ↑ Vorgerd et al: muscle glycogenoses. In: Deutsches Ärzteblatt . 2002; 36, pp. 2328-2340. [1]
6. ↑ Quinlivan & Beynon: Pharmacological and nutritional treatment trials in McArdle disease. In: Acta Myol. 2007; 26 (1), pp. 58-60. PMID 17915572
7. ↑ Maté-Muñoz et al .: Favorable responses to acute and chronic exercise in McArdle patients. In: Clin J Sport Med. 2007; 17 (4), pp. 297-303. PMID 17620784
8. ↑ Vorgerd include: Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. In: Arch Neurol . 2000; 57 (7), pp. 956-963. PMID 10891977 (full text)

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !