X-linked creatine deficiency

Alternate names

Mental retardation , X-linked with seizures, short stature and midface hypoplasia; Mental retardation , X-linked, with creatine transport deficiency; X-linked creatine transporter deficiency; X-linked creatine deficiency syndrome; Creatine deficiency, X-linked

Definition

X-linked creatine deficiency primarily affects development of the brain and nervous system.

Summary

People with this disorder have intellectual disability, which can range from mild to severe, and delayed speech development. Some affected individuals develop behavioral disorders such as attention-deficit/hyperactivity disorder (ADHD) or autistic behaviors that affect communication and social interaction.

Onset

Symptoms can begin at any age, but usually begin in early childhood.

Epidemiology

The prevalence of X-linked creatine deficiency is unknown. More than 150 affected individuals have been identified. The disorder has been estimated to account for between 1 and 2 percent of males with intellectual disability.

Cause

Mutations in the SLC6A8 gene cause X-linked creatine deficiency. The SLC6A8 gene provides instructions for making a protein that transports the compound creatine into cells. Creatine is needed for the body to store and use energy properly.

Gene mutation SLC6A8 gene mutations impair the ability of the transporter protein to bring creatine into cells, resulting in a creatine shortage (deficiency). The effects of creatine deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.

Inheritance

This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may or may not cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In most cases of X-linked inheritance, males experience more severe symptoms of the disorder than females. About half of females with one mutated copy of the SLC6A8 gene in each cell have intellectual disability, learning difficulties, or behavioral problems. Other females with one mutated copy of the SLC6A8 gene in each cell have no noticeable neurological problems.

Symptoms

The following list includes the most common signs and symptoms in people with X-linked creatine deficiency. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:

• Intellectual disability
• Delayed speech and language development
• Behavioral issues
• Seizures
• Low muscle tone (hypotonia)
• Uncoordinated movement (ataxia)
• Gastrointestinal symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal circulating creatine concentration(Abnormality of creatine metabolism)
• Delayed speech and language development(Deficiency of speech development)
• Global developmental delay
• Intellectual disability(Mental deficiency)
• Seizure

30%-79% of people have these symptoms

• Aganglionic megacolon(Enlarged colon lacking nerve cells)
• Ataxia
• Athetosis(Involuntary writhing movements in fingers, hands, toes, and feet)
• Autistic behavior
• Cachexia(Wasting syndrome)
• Chorea
• Constipation
• Dystonia
• Hyperactivity(More active than typical)
• Hypertonia
• Ileus
• Malar flattening(Zygomatic flattening)
• Muscular hypotonia(Low or weak muscle tone)
• Open mouth(Gaped jawed appearance)
• Self-mutilation(Deliberate self-harm)
• Short stature(Decreased body height)

5%-29% of people have these symptoms

• Joint hyperflexibility(Joints move beyond expected range of motion)
• Mask-like facies(Expressionless face)
• Microcephaly(Abnormally small skull)
• Ptosis(Drooping upper eyelid)
• Redundant skin(Loose redundant skin)

Diagnosis

X-linked creatine deficiency is diagnosed based on the symptoms, clinical exam, and the results of genetic testing. Screening tests looking for levels of specific chemicals in the urine are often used prior to genetic testing.

Treatment

Treatment for X-linked creatine deficiency is focused on managing the symptoms. Specialists involved in the care of someone with X-linked creatine may include:

• Neurologist
• Speech/language pathologist
• Occupational therapy
• Physical therapy

NIH genetic and rare disease info

• NIH info on X-linked creatine deficiency

X-linked creatine deficiency is a rare disease.

X-linked creatine deficiency Resources
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