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

• X-Linked Creatine Deficiency Syndrome
• X-Linked Creatine Transporter Deficiency Disorder
• X-Linked Mental Retardation with Seizures, Short Stature and Midface Hypoplasia

What is X-Linked Creatine Deficiency Disorder? (Definition/Background Information)

• X-Linked Creatine Deficiency Disorder is a rare condition that primarily affects the brain. Signs and symptoms generally develop before age 2 and may include mild to severe intellectual disability; delayed speech development, behavioral problems (i.e. autistic features, hyperactivity), and seizures
• Less commonly, affected people may have distinctive facial features, heart abnormalities, and gastrointestinal disorders
• X-Linked Creatine Deficiency Disorder is caused by changes (mutations) in the SLC6A8 gene and is inherited in an X-linked manner
• Treatment with high doses of creatine monohydrate, L-arginine, and L-glycine has been used to treat some of the symptoms associated with X-Linked Creatine Deficiency Disorder with variable success

(Source: X-Linked Creatine Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets X-Linked Creatine Deficiency Disorder? (Age and Sex Distribution)

• X-Linked Creatine Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for X-Linked Creatine Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since X-Linked Creatine Deficiency Disorder can be inherited
• Currently, no risk factors have been clearly identified for this deficiency 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 X-Linked Creatine Deficiency Disorder? (Etiology)

• X-Linked Creatine Deficiency Disorder is caused by changes (mutations) in the SLC6A8 gene and is inherited in an X-linked manner

(Source: X-Linked Creatine Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of X-Linked Creatine Deficiency Disorder?

The signs and symptoms of X-Linked Creatine Deficiency Disorder may include:

• Abnormality of metabolism/homeostasis
• Aggressive behavior
• Attention deficit hyperactivity disorder
• Broad forehead
• Delayed myelination
• Exotropia
• Feeding difficulties in infancy
• Generalized hypotonia
• Hypermetropia
• Impaired social interactions
• Joint hypermobility
• Midface retrusion
• Neonatal hypotonia
• Pes cavus
• Poor hand-eye coordination
• Underfolded superior helices
• Vomiting

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of creatine metabolism
• Delayed speech and language development
• Intellectual disability
• Seizures

Frequently present symptoms in 30-79% of the cases:

• Aganglionic megacolon
• Ataxia
• Athetosis
• Autistic behavior
• Cachexia
• Chorea
• Constipation
• Hyperactivity
• Hypertonia
• Ileus
• Malar flattening
• Open mouth
• Self-mutilation

Occasionally present symptoms in 5-29% of the cases:

• Joint hyperflexibility
• Mask-like facies
• Microcephaly
• Redundant skin

(Source: X-Linked Creatine Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is X-Linked Creatine Deficiency Disorder Diagnosed?

X-Linked Creatine 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 studies, if necessary

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 X-Linked Creatine Deficiency Disorder?

The complications of X-Linked Creatine Deficiency Disorder may include:

• Severe behavioral issues
• Weak muscles and joints
• Intellectual impairment

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

How is X-Linked Creatine Deficiency Disorder Treated?

There is no cure for X-Linked Creatine Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can X-Linked Creatine Deficiency Disorder be Prevented?

Currently, X-Linked Creatine Deficiency 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
• 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 X-Linked Creatine Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of X-Linked Creatine Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for X-Linked Creatine Deficiency Disorder:

• X-Linked Creatine Deficiency Disorder is also known by the following names: X-Linked Mental Retardation with Creatine Transport Deficiency

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

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