What are the other Names for this Condition? (Also known as/Synonyms)

• Glycogen Storage Disease due to Muscle Phosphorylase Kinase Deficiency
• Glycogenosis due to Muscle Phosphorylase Kinase Deficiency
• Muscle PhK Deficiency disorder

What is Muscular Phosphorylase Kinase Deficiency Disorder? (Definition/Background Information)

• Glycogen Storage Disease due to Muscle Phosphorylase Kinase (PhK) Deficiency is a benign inborn error of glycogen metabolism characterized by exercise intolerance
• The disease starts generally in adolescence or adulthood. Patients may present with exercise intolerance with myalgia, cramps, fatigue, and sometimes myoglobinuria. In some cases, patients may present with progressive muscle weakness.
• Symptoms are usually mild, and myopathy may be asymptomatic. A neonatal form with generalized muscular hypotonia and respiratory insufficiency has also been described

(Source: Glycogen storage disease due to muscle phosphorylase kinase deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Muscular Phosphorylase Kinase Deficiency Disorder? (Age and Sex Distribution)

• Muscular Phosphorylase Kinase Deficiency Disorder is a very rare congenital disorder, described in less than 30 individuals in the medical literature
• The presentation of symptoms generally begins in adolescence or adulthood. However, rarely, newborns may be affected by a subtype of this disorder
• The condition predominantly occurs in males
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Muscular Phosphorylase Kinase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Muscular Phosphorylase Kinase Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Muscular Phosphorylase Kinase Deficiency Disorder? (Etiology)

Muscular Phosphorylase Kinase Deficiency Disorder is caused by mutation(s) in PHKA1 gene.

• This gene codes for alpha subunit of phosphorylase kinase, an enzyme that is necessary for the activation of another enzyme known as glycogen phosphorylase and thus plays a crucial role in the regulation of glycogenolysis 
• The condition is inherited in an X-linked manner

X-linked recessive pattern of inheritance: The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

What are the Signs and Symptoms of Muscular Phosphorylase Kinase Deficiency Disorder?

The signs and symptoms of Muscular Phosphorylase Kinase Deficiency Disorder may include the following, associated with physical exertion:

• Muscle pain 
• Cramps
• Fatigue 
• Myoglobinuria (presence of myoglobin in urine)
• Low muscle tone in newborns
• Respiratory distress in newborns

How is Muscular Phosphorylase Kinase Deficiency Disorder Diagnosed?

Muscular Phosphorylase Kinase Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy of muscle tissue to measure phosphorylase kinase activity 
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Muscular Phosphorylase Kinase Deficiency Disorder?

The complications of Muscular Phosphorylase Kinase Deficiency Disorder may include:

• Progressive muscle weakness
• Low self-esteem due to inability to exercise rigorously 

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Muscular Phosphorylase Kinase Deficiency Disorder Treated?

There is no cure for Muscular Phosphorylase Kinase Deficiency Disorder, since it is a genetic condition. In general, individuals affected by this disorder do not require treatment.

How can Muscular Phosphorylase Kinase Deficiency Disorder be Prevented?

Currently, Muscular Phosphorylase Kinase Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Avoiding rigorous physical activities and resorting to moderate exercise may help affected individuals minimize the symptoms of this condition
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Muscular Phosphorylase Kinase Deficiency Disorder? (Outcomes/Resolutions)

The prognosis of Muscular Phosphorylase Kinase Deficiency Disorder is good, since the condition is benign and may cause preventable symptoms in most cases.

Additional and Relevant Useful Information for Muscular Phosphorylase Kinase Deficiency Disorder:

Muscular Phosphorylase Kinase Deficiency is also known by the following names:

• Glycogen Storage Disease 9D (GSD 9D)
• Glycogen Storage Disease 9E (GSD 9E)
• Glycogen Storage Disease Type IXd (GSD IXd)
• Glycogen Storage Disease Type IXe (GSD IXe)
• Glycogenosis Type 9D
• Glycogenosis Type 9E
• Muscle PhK Deficiency disorder

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/