Clinical Guidance

Several studies in European populations have not found an association between severity of clinical findings and PYGM genotype .

Source: GeneReviews — "Glycogen Storage Disease Type V"

Diagnostic Criteria

Suggestive Findings

Glycogen storage disease type V should be suspected in individuals with the following supportive findings.

Clinical findings

Source: GeneReviews — "Glycogen Storage Disease Type V"

Differential Diagnosis

The differential diagnosis of glycogen storage disease type V (GSDV) includes mitochondrial myopathy (mitochondrial myopathy is genetically heterogeneous [see Mitochondrial Disorders Overview]) and the disorders associated with the genes listed in . Because most of the disorders in have different forms (i.e., hepatic and muscle), information included in the table pertains to the myopathic forms that are usually manifest in children or adults. For the purposes of differential diagnosis, clinicians should be aware that the second-wind phenomenon is virtually pathognomonic for GSDV.

Table 2.

Other Genes of Interest in the Differential Diagnosis of Glycogen Storage Disease Type V (GSDV)

Gene(s)1 | DiffDx Disorder | MOI | Clinical Features of DiffDx Disorder

Source: GeneReviews — "Glycogen Storage Disease Type V"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with glycogen storage disease type V (GSDV), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Physical examination with emphasis on muscle strength/weakness

• Basal serum CK activity

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Currently, simple healthy lifestyle interventions (i.e., following a diet rich in complex carbohydrates and regular exercise practice), the most effective means of preventing and managing exercise intolerance in GSDV, require a proactive attitude of clinicians, exercise professionals, and patient advocates . The benefits of a professionally supervised exercise program are safety and ease of implementation. Patients with GSDV generally adapt well to regular exercise; training should be designed to ensure gradual progression of exercise intensity, especially in the more severely affected patients. For children, it is important to provide parents, caregivers, and educators (especially physical education teachers) with appropriate information to ensure their best possible management. Patients who commit to a supervised, gradual exercise program are able to improve their fitness levels almost as effectively as healthy individuals. Indeed, affected individuals may become virtually asymptomatic during activities of daily living.

Source: GeneReviews — "Glycogen Storage Disease Type V"

Clinical Guidance

Exercises that should be avoided in patients with GSDV are the following:

• Static muscle contractions (e.g., handgrip exercises)

• Static muscle contractions or heavy loads on low muscle mass (e.g., weight lifting), unless performed under programmed supervision of clinicians and exercise/fitness specialists

• Dynamic exercises at a high-intensity level (e.g., competitive ball games)

• Exercises with a high involvement of eccentric (lengthening) muscle contractions (e.g., jumps)

• Very intense dynamic aerobic exercise (e.g., running, strenuous swimming, or cycling) except in very fit individuals who are also well trained for the specific activity

General anesthetics. Risk of acute muscle damage is reported with certain general anesthetics (usually muscle relaxants and inhaled anesthetics), although in practice, problems appear to be rare. Nonetheless, measures for preventing muscle ischemia and rhabdomyolysis should be taken in individuals with GSDV .

Source: GeneReviews — "Glycogen Storage Disease Type V"

Therapies Under Investigation

Preclinical studies (animal models) have shown that sodium valproate, a histone deacetylase inhibitor, (1) increases GP expression in muscle fibers from McArdle sheep and (2) induces the expression of the brain isoenzyme, GP-BB, with a decrease of glycogen accumulation in primary skeletal muscle cultures derived from a McArdle knock-in mouse . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Glycogen Storage Disease Type V"

Surveillance Guidelines

Appropriate surveillance includes the following:

• Annual routine physical examination

• Annual review of diet

Source: GeneReviews — "Glycogen Storage Disease Type V"